Original Article |
Corresponding author: Rada M. Markova ( rada_markova@yahoo.com ) © 2023 Rada M. Markova, Iren S. Tzotcheva, Penka Perenovska, Atanas Mangarov, Lubomira Nikolaeva-Glomb, Veselin Hadjiev.
This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 4.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Citation:
Markova RM, Tzotcheva IS, Perenovska P, Mangarov A, Nikolaeva-Glomb L, Hadjiev V (2023) Efficacy and safety of Aviron Rapid® in adolescents and children with viral acute upper respiratory tract infection: a multi-center, randomized, double blind, placebo-controlled clinical trial. Folia Medica 65(4): 546-568. https://doi.org/10.3897/folmed.65.e108153
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Introduction: Acute upper respiratory tract infections (AURTIs) are associated with a significant burden on society attributed to medical care and loss of productivity. Novel therapies that are able to shorten disease duration, while providing symptom relief and being well tolerated, are an unmet medical need.
Aim: The main objective of this trial was to investigate the efficacy and safety of Aviron Rapid, a dietary supplement containing andrographolide, proprietary spirulina, and humic acid, in the management of AURTIs in adolescents and children.
Materials and methods: This randomized, double-blind, placebo-controlled trial was conducted between January 2020 and March 2020 in 85 general practitioner practices in Bulgaria. Adolescents (13–17 years) and children (5–12 years) with a clinical diagnosis of AURTI were randomly assigned to receive standard symptomatic therapy + Aviron Rapid or placebo for 5 and 7 days, respectively. The primary endpoints of this trial were the number (and percentage) of clinically recovered patients and the mean disease duration.
Results: In total, 380 adolescents and 401 children were enrolled in 2 age cohorts and randomly assigned to treatment with Aviron Rapid or placebo. The percentage of patients meeting the criteria for clinical recovery was significantly higher in the Aviron Rapid group compared with the placebo group from 24 and 48 hours after initiation of treatment in adolescents and children, respectively. Aviron Rapid treatment significantly reduced the duration of disease, of fever, and of antipyretics intake in both adolescents and children. When compared to placebo, a significantly higher percentage of adolescents and children on Aviron Rapid achieved a persistent decrease in temperature of less than 37°C as soon as 24 hours after starting treatment. Overall, a low number of adverse events was reported and no major differences in the incidence of individual adverse events were observed between the two treatment groups in both cohorts.
Conclusions: This clinical trial demonstrated the efficacy of Aviron Rapid in the management of acute upper respiratory tract infections in adolescents and children. Aviron Rapid treatment rapidly increased the number of clinically recovered patients and reduced overall disease duration and duration of symptoms, in particular fever, while being well tolerated.
Trial registration: International Standard Randomised Controlled Trial Number (ISRCTN) 12221500. Retrospectively registered on 29 March 2022. [https://doi.org/10.1186/ISRCTN12221500]
antivirals, acute upper respiratory tract infections, andrographolide, proprietary spirulina, humic acid
AE adverse event
AURTI acute upper respiratory tract infection
CI confidence interval
FPS-R modified face pain scale
GP general practitioner
VAS visual analogue scale
acute upper respiratory tract infections (AURTIs) are associated with a significant burden of disease. Easy airdrop transmission, short incubation time, and short-lived specific immunity contribute to more than 17 billion incident cases worldwide in 2019, resulting in a considerable non-fatal burden as the symptoms may significantly affect quality of life and productivity.[
Aviron Rapid® is a dietary supplement consisting of andrographolide, proprietary spirulina extract, and humic acid racemic mixture[
The main objective of this trial was to evaluate the efficacy and safety of Aviron Rapid in patients with a viral AURTI clinically diagnosed by their general practitioner (GP) and treated according to standard medical practice.
This was a multi-center, Phase 4, randomized, double-blind, placebo-controlled clinical trial with Aviron Rapid in patients with a viral AURTI, recruited from 85 GP practices in Bulgaria between January 27 and March 9, 2020. The trial included 3 age cohorts: adults (18–60 years), adolescents (13–17 years; also referred to as ‘the adolescent cohort’), and children (5–12 years; also referred to as ‘the pediatric cohort’). Informed consent was obtained from all participants participating in the study. Efficacy and safety data of the adult cohort in this trial have been reported previously.[
Male and female adolescents (13–17 years, both inclusive) and children (5–12 years, both inclusive) with a clinical diagnosis of a viral AURTI were enrolled in the trial. Diagnosis by the GP was based on 1) an axillary temperature of more than 37.0°C and 2) presence of one or more of the following symptoms with onset of the first symptom within 24 hours before screening: nasal congestion, cough, sore throat, headache, fatigue, and sleep disturbance. Patients with clinical symptoms of severe flu or AURTI requiring hospitalization, or with symptoms similar to AURTI but related to other underlying diseases (infectious diseases, flu-like syndrome in systemic connective tissue disease, onco-hematologic, and other diseases) were excluded. Other exclusion criteria focused on past or current use of medications or medical disorders that could potentially confound trial results or interfere with safe completion of the trial.
Adolescents and children presenting to a GP practice with symptoms suggestive of viral AURTIs were clinically examined (including measurement of axillary temperature) by the GP on day 1 and, if eligible, were enrolled and randomly assigned (1:1) to receive active treatment or placebo in a double-blinded fashion. Patients in the active group (Group 1) received standard symptomatic therapy + Aviron Rapid, patients in the placebo group (Group 2) received standard symptomatic therapy + placebo.
Randomization of patients was done using software designed by an external, independent vendor and was stratified by center. The active and placebo treatments were packed in blisters and delivered to the GP practices in white paper boxes, labeled with unique treatment codes. Manufacturing, packaging, and labeling were performed by the sponsor of the trial. Patients, GPs, and the sponsor’s project team were blinded to treatment group assignments throughout the trial and until database lock.
On day 1, patients or their parents were given a diary to record axillary temperature, antipyretics intake, symptom severity, and recovery status twice daily with 12-hour intervals (once in the morning, once in the evening) during the treatment period, i.e., days 1 to 5 for adolescents and days 1 to 7 for children. Adolescents recorded data in the diary under supervision of their parents. For children, data was recorded by the parents. After the end of treatment, on day 6 (adolescents) or day 8 (children), patients returned to the GP practice for a closing visit. During this visit, the GP clinically examined (including measurement of axillary temperature) the patient and verified completeness of the data recorded in the diary. In addition, on day 1, symptom severity was assessed and on day 6, a general evaluation of the patient’s condition (recorded as ‘healthy’ or ‘ill’) was performed.
Aviron Rapid was provided as 647-mg tablets for oral use containing 10 mg andrographolide, 100 mg proprietary spirulina extract, and 250 mg proprietary humic acid racemic mixture. Placebo was provided as tablets visually matching the Aviron Rapid tablets. Patients were treated according to the following schedule: adolescents: 3 tablets 3 times daily on day 1, 2 tablets 3 times daily on day 2, and 1 tablet 3 times daily on days 3 to 5; children: 2 tablets 3 times daily on day 1 and 1 tablet 3 times daily on days 2 to 7. Tablets were taken with water, in the morning, at noon, and in the evening. Standard symptomatic therapy included non-steroidal anti-inflammatory drugs, decongestants, bronchodilators, mucolytics, antitussives, and other drugs for treatment of chronic diseases. Use of other antiviral remedies, antihistamines, antibiotics, and interferons was not allowed.
The primary endpoints of this trial were the number (and percentage) of clinically recovered patients and the mean disease duration. Patients were considered clinically recovered if the following 3 criteria were met: 1) persistent improvement of every symptom to “very mild” or “lack of symptoms” (severity score <2 as measured on a visual analogue scale [VAS] for adolescents or a modified face pain scale [FPS-R] for children) until the end of follow-up and a total severity score for all symptoms [i.e. the sum of the 6 individual symptom severity scores] <12 points; 2) persistent decrease of the axillary temperature to <37.0°C, i.e. temperature <37.0°C at 2 consecutive measurements with a 12-hour interval and no new increase >37°C (i.e., fever) until the end of follow-up; 3) the decrease in axillary temperature <37°C was achieved without the use of antipyretics. The severity of the symptoms nasal congestion, cough, sore throat, headache, fatigue, and sleep disturbance was measured using a VAS (for adolescents) or FPS-R (for children) ranging from 0 to 10 with 0 = lack of symptoms and 10 = very severe symptoms. Disease duration was defined as the interval between treatment initiation and the time point at which the patient met the criteria for clinically recovery. The primary endpoints were assessed twice daily with 12-hour intervals during the treatment period (days 1 to 5 for adolescents or days 1 to 7 for children) and recorded in the patient’s diary.
Secondary efficacy endpoints included number (and percentage) of patients with persistent decrease of the axillary temperature <37.0°C without the use of antipyretics, mean time to persistent decrease of the axillary temperature <37.0°C, number (and percentage) of patients taking antipyretics, mean duration of antipyretic treatment, mean total severity score for all symptoms, number (and percentage) of patients with persistent improvement of a particular symptom (severity score <2), and number (and percentage) of patients considered fully recovered. Patients were considered fully recovered if at 2 consecutive measurements with a 12-hour interval they scored 2 or 3 on a scale ranging from 1 to 3 with 1 = I still feel ill; 2 = I feel better; 3 = I feel healthy. Secondary efficacy endpoints were assessed twice daily at 12-hour intervals and recorded in the patient’s diary from day 1 to the end of treatment (day 5 [adolescents] or day 7 [children]) for axillary temperature, antipyretics intake, and symptom-related endpoints, and from day 1 to the closing visit (day 6 [adolescents] or day 8 [children]) for full recovery status.
Safety-related endpoints included the incidence of adverse events (AEs), as recorded in the patient’s diary during the treatment period, and physical examinations by the GP on days 1 and 6 (adolescents) or 8 (children).
The statistical analyses were done by an external blinded statistician. In both cohorts, a total number of 320 patients (160 per treatment group) were required to detect a difference of 5% between the two treatment groups with 80% power.
All patients who completed the treatment and all planned trial visits per protocol and did not have protocol deviations were included in the efficacy analyses. For the primary endpoint analysis, the 2-proportion Z-test was used to compare the percentages of clinically recovered patients between the active and placebo group. The mean disease duration in both groups was compared using an independent samples t-test. The secondary endpoints were analyzed using the same statistical methods as used for the primary endpoint analyses.
The safety analysis included all patients who received at least one dose of Aviron Rapid or a placebo. The incidence of AEs was summarized descriptively. All statistical tests were two-sided except for the 2-proportion Z-test. Statistical significance was set at p<0.05. All statistical analyses were performed using SPSS 17.
The trial started on 27 January 2020 (i.e., enrolment of the first patient in the trial) and was completed on 14 March 2020 (i.e., end of follow-up for the last patient in the trial). In total, 380 adolescents and 401 children were enrolled in the respective cohorts and randomly assigned to one of the two treatment groups. Safety analyses included all randomized patients. Efficacy analyses comprised 329 adolescents and 319 children. The reasons for excluding patients from the efficacy analysis are shown in Fig.
Overall, in the adolescent cohort, the mean age was 14.6 years and 54% of patients were male. In the pediatric cohort, the mean age was 8.6 years and 51% of patients were male. Patient demographics were comparable in the two treatment groups in both cohorts. The total symptom severity score at baseline was slightly higher in the adolescent cohort (25.6 and 24.9 in the active and placebo group, respectively) compared with the pediatric cohort (24.6 and 23.5, respectively). The mean axillary temperature was 38°C in the active and placebo groups in both cohorts. The percentages of patients reporting any symptom at baseline were generally lower in the pediatric cohort, compared with the adolescent cohort. Nasal congestion was the most common symptom in both cohorts (reported in >91% of adolescents and >88% of children). There were no significant differences between the active and placebo group in both cohorts (Table
For nasal congestion, cough, sore throat, headache, fatigue, and sleep disturbance, n (%) refers to the number (and percentage) of patients with a particular symptom at baseline; the mean values refer to the mean severity of a particular symptom at baseline.
Patient disposition (Safety Analysis). Safety analysis included all patients who received at least one dose of Aviron Rapid or placebo. Efficacy analysis included all patients who completed treatment and all planned trial visits per protocol, and did not have protocol deviations.
Parameter | Statistics | Adolescents (13-17 years) | Children (5-12 years) | ||
Active (Aviron Rapid) (n=172) | Placebo (n=157) | Active (Aviron Rapid) (n=161) | Placebo (n=158) | ||
Age (years) | Mean | 14.58 | 14.59 | 8.83 | 8.42 |
95% CI | (14.29, 14.71) | (14.28, 14.72) | (8.50, 9.16) | (8.07, 8.75) | |
Male | n (%) | 91 (52.9%) | 87 (55.4%) | 76 (47.2%) | 86 (54.4%) |
Total symptom severity score | Mean | 25.6 | 24.9 | 24.6 | 23.5 |
95% CI | (24.13, 27.10) | (23.28, 26.52) | (23.10, 26.10) | (21.93, 25.10) | |
Axillary temperature (°C) | Mean | 38.15 | 38.11 | 38.09 | 38.23 |
95% CI | (38.05, 38.25) | (38.01, 38.21) | (38.14, 38.34) | (38.00, 38.21) | |
Nasal congestion | n (%) | 160 (93.0%) | 143 (91.1%) | 148 (91.9%) | 140 (88.6%) |
Mean | 4.71 | 4.67 | 5.01 | 4.76 | |
Cough | n (%) | 155 (90.1%) | 142 (90.4%) | 139 (86.3%) | 142 (89.9%) |
Mean | 4.74 | 4.90 | 5.25 | 4.65 | |
Sore throat | n (%) | 164 (95.3%) | 151 (96.2%) | 129 (80.1%) | 125 (79.1%) |
Mean | 5.22 | 5.19 | 5.36 | 5.62 | |
Headache | n (%) | 163 (94.8%) | 143 (91.1%) | 122 (75.8%) | 129 (81.6%) |
Mean | 4.83 | 4.63 | 4.87 | 4.79 | |
Fatigue | n (%) | 164 (95.3%) | 149 (94.9%) | 145 (90.1%) | 139 (88.0%) |
Mean | 5.48 | 5.25 | 5.19 | 4.98 | |
Sleep disturbance | n (%) | 114 (66.3%) | 108 (68.8%) | 109 (67.7%) | 89 (56.3%) |
Mean | 3.26 | 2.88 | 3.47 | 3.12 |
In the adolescent cohort, the percentages of patients meeting the criteria for clinical recovery were consistently higher in the active group compared with the placebo group from 24 hours after initiation of treatment (i.e., morning of day 2: 8.1% versus 1.9%, respectively; p=0.0055) until the end of treatment (i.e., evening of day 5: 90.7% versus 80.9%; p=0.0052). Differences were statistically significant (p<0.05) as of the morning of day 2 onwards until end of treatment, except for the morning of day 4 (p=0.0786) (Fig.
Similar results were obtained in the pediatric cohort with consistently higher percentages of clinically recovered patients in the active group compared with the placebo group from 24 hours after initiation of treatment (i.e., morning of day 2: 5.6% versus 4.4%, respectively; p=0.31) until end of treatment (i.e., evening of day 7: 98.8% versus 89.2%; p=0.001). Differences were statistically significant (p<0.05) as of the morning of day 3 and throughout the treatment period (Fig.
Primary endpoint: percentage clinically recovered patients (Efficacy Analysis). P-values from 1-sided 2-proportion Z-test.
Persistent decrease of temperature
From the morning of day 2 onwards until the end of treatment, the percentage of patients in the adolescent and pediatric cohorts with a persistent temperature decrease of <37°C was consistently higher in the active group than that in the placebo group, with the biggest difference between the two treatment groups being noticed on the morning of day 5 in adolescents (90.7% versus 77.7%; p<0.001) and on the evening of day 3 in children (58.4% versus 38.6%; p=0.001) (Fig.
The percentage of adolescent patients taking antipyretics was consistently lower in the active group compared with the placebo group from the evening of day 1 onwards until the end of treatment. In the pediatric cohort, statistically significantly lower percentages of patients on antipyretics were observed as of the morning of day 3 until the end of treatment (Fig.
Secondary endpoints: Percentage of patients with persistent decrease of temperature <37°C (Efficacy Analysis). P-values from 1-sided 2-proportion Z-test.
Secondary endpoints: mean time to persistent decrease of temperature <37°C (Efficacy Analysis). P-values from 2-sided independent samples T-test.
Secondary endpoints: percentage of patients taking antipyretics (Efficacy Analysis). P-values from 1-sided 2-proportion Z test for adolescents and 2-sided Pearson chi-square test for children.
Secondary endpoints: mean duration of antipyretics intake (Efficacy Analysis). P-values from 2-sided independent samples T-test.
Adolescents (13-17 years) | Children (5-12 years) | |||
Active (Aviron Rapid) (n=192) | Placebo (n=188) | Active (Aviron Rapid) (n=203) | Placebo (n=198) | |
Any adverse event, n (%) | 14 (7.3%) | 23 (12.2%) | 30 (14.8%) | 27 (13.6%) |
Antibiotic treatment for unknown reason | 13 (6.8%) | 17 (9.0%) | 20 (9.9%) | 18 (9.1%) |
Bronchitis | 0 (0%) | 2 (1.1%) | 6 (3.0%) | 4 (2.0%) |
Hospitalization | 1 (0.5%) | 0 (0%) | 2 (1.0%) | 2 (1.0%) |
Otitis | 0 (0%) | 2 (1.1%) | 1 (0.5%) | 1 (0.5%) |
Laryngitis | 0 (0%) | 1 (0.5%) | 1 (0.5%) | 0 (0%) |
Acute tonsillitis | 0 (0%) | 1 (0.5%) | 0 (0%) | 1 (0.5%) |
Allergic reaction | 0 (0%) | 0 (0%) | 0 (0%) | 1 (0.5%) |
The mean total severity of clinical symptoms in the adolescents in the active group was consistently lower than that in the placebo group from the evening of day 1 until the end of treatment, with day 3 showing the biggest difference between the two groups (Supplementary Table 4) (see Appendix). For nasal congestion, cough, and sleep disturbance, the percentages of adolescents with persistent improvement were consistently higher in the active group compared with the placebo group throughout the entire treatment period. As of the morning of day 2 until the end of treatment, a higher percentage of patients in the active group had persistent improvement of sore throat compared with the placebo group. No relevant differences between the two groups were observed for headache and fatigue (Supplementary Tables 5–10) (see Appendix).
Among children in the active group, the mean total severity of clinical symptoms was consistently lower than that of the placebo group as of the morning of day 3 until the end of treatment. Before that time point, the mean total score was higher in the placebo group (Supplementary Table 4) (see Appendix). A similar pattern was observed for the individual symptoms nasal of congestion and cough, for which statistically significantly higher percentages of children with persistent improvement in the active group were only observed from day 5 (for nasal congestion) or day 6 (for cough) onwards. For fatigue, sore throat, and sleep disturbance, the percentages of children with persistent improvement were consistently higher in the active group compared with the placebo group as of the evening of day 1 or the morning of day 2 and throughout the entire treatment period. The largest difference between the two groups was observed on days 3 and 4 for fatigue and sleep disturbance, and on days 4 and 5 for sore throat. For headache, similar percentages were observed in both groups throughout the treatment period until the morning of day 6. As of the evening of day 6 until the end of treatment, significantly higher percentages of patients in the active group had persistent improvement of headache compared with the placebo group (Supplementary Tables 5–10) (see Appendix).
The percentage of adolescents and children being considered fully recovered was consistently higher in the active group as of the evening of day 2 or the evening of day 1, respectively, until nearly all patients in both groups reached full recovery by the end of treatment (Supplementary Table 11) (see Appendix).
In both cohorts, the incidence of AEs was similar in the active and placebo groups. No serious AEs were reported. In the adolescent cohort, 14 (7.3%) patients in the active group and 23 (12.2%) in the placebo group reported AEs, the most common being antibiotic treatment for unknown reason (reported in 13 [6.8%] and 17 [9.0%] patients, respectively). In the pediatric cohort, 30 (14.8%) and 27 (13.6%) patients in the active and placebo group, respectively, reported AEs, the most common also being antibiotic treatment for unknown reason (in 20 [9.9%] and 18 [9.1%] patients, respectively) (Table
Acute upper respiratory tract infections are a major cause of morbidity and one of the most frequent reasons for children and adults to visit GP offices. Given that the majority of AURTIs have a viral etiology, their management is often limited to symptomatic medications. However, there is no conclusive evidence that these medications also shorten symptom duration.[
This clinical trial demonstrated that daily use of Aviron Rapid for 5 (adolescents) or 7 (children) days in combination with standard symptomatic therapy resulted in a significantly shorter duration of disease compared with placebo. The percentage of clinically recovered patients was significantly higher in adolescents and children on Aviron Rapid than in those on placebo from 24 and 48 hours after start of treatment, respectively. Aviron Rapid intake significantly reduced the duration of fever (i.e., an axillary temperature >37°C) and the duration of antipyretics intake. As early as 24 hours after start of treatment, a significantly higher percentage of adolescents and children on Aviron Rapid achieved persistent decrease of temperature <37°C. The effect of Aviron Rapid treatment on symptom relief was generally more pronounced in adolescents than in children. Remarkably, throughout the entire treatment period, a higher percentage of adolescents on Aviron Rapid experienced relief of nasal congestion, cough, and sleep disturbance compared with placebo. In children, a similar beneficial effect on nasal congestion and cough was observed, though it became apparent later in the course of disease (i.e. by days 5 and 6, respectively). The largest difference in percentage of patients with relief of sore throat between the Aviron Rapid and placebo group was observed on days 3 and 4 for adolescents and on days 4 and 5 for children.
Across both cohorts, a low number of AEs was reported and no major differences in the incidence of individual AEs were observed between the two treatment groups.
The results of this trial confirm the promising results previously obtained with Aviron Rapid in adults[
Given that the standard approach to managing AURTIs in contemporary outpatient practice does not include testing to identify the infectious agent, one limitation of this trial was the lack of confirmation of the viral etiology of the AURTIs. Moreover, it cannot be guaranteed that the trial included only patients who visited their general practitioner’s office within 24 hours of the onset of their first symptom. Another limitation of the trial was the relatively small sample size.
The results of this trial in adolescents and children confirms previous data reporting on the efficacy of Aviron Rapid, a dietary supplement containing andrographolide, proprietary spirulina extract, and humic acid, in the management of AURTIs in adults. Aviron Rapid treatment rapidly increased the number of clinically recovered patients and reduced overall disease duration and duration of symptoms, in particular fever, while being well tolerated.
The trial protocol and informed consent were approved by the Ethics Committee of the First Pediatric Consultative Clinic, Ltd, Bulgaria (on November 30, 2019, ref No. 033/30.10.2019). The trial was conducted in accordance with the Declaration of Helsinki, the protocol, the International Council for Harmonisation for Good Clinical Practice Guideline E6 (R2), and local ethical and legal requirements. Written informed consent was obtained from all patients’ parents prior to trial entry.
Not applicable
The dataset supporting the conclusions of this article is included within the article (and the Supplementary Tables).
The authors declare that they have no competing interests.
This trial was funded by Neopharm Bulgaria Ltd. The funder of the trial had no role in the trial design, data collection, data analysis, data interpretation, or writing of the manuscript.
Conceptualization of the trial: R.M.M., I.S.T, and L.N.; Trial methodology: R.M.M., I.S.T, and L.N.; Investigation of participants: R.M.M., I.S.T, P.P., and A.M.; Supervision of the trial: R.M.M. and I.S.T.; Validation of trial data: P.P. and R.M.M.; Project administration: A.M.; Visualization of trial data: I.S.T., R.M.M., and P.P.; Resources: L.N.; Data curation, Formal analysis, Software: V.H. All authors contributed to data analysis, drafting, and revising the manuscript. All authors reviewed and approved the final manuscript.
Medical writing support was provided by Ans Rombout, Emtex Life Science, Belgium. The authors would like to thank all GPs and patients (and their parents) who participated in the trial.
Supplementary tables
Additional tables which present results of the trial not included in the body of the manuscript.
Primary endpoint: number and percentage of clinically recovered patients (Efficacy Analysis)
Time Point | Active (Aviron Rapid) | Placebo | P-valuea | ||
n cumulative | % cumulative | n cumulative | % cumulative | ||
Adolescents (13-17 years) | N=172 | N=157 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 0 | 0.0 | 0 | 0.0 | - |
Day 2 - morning | 14 | 8.1 | 3 | 1.9 | 0.0055 |
Day 2 - evening | 24 | 14.0 | 8 | 5.1 | 0.0033 |
Day 3 - morning | 42 | 24.4 | 23 | 14.6 | 0.0128 |
Day 3 - evening | 58 | 33.7 | 37 | 23.6 | 0.0217 |
Day 4 - morning | 89 | 51.7 | 69 | 43.9 | 0.0786 |
Day 4 - evening | 112 | 65.1 | 88 | 56.1 | 0.0474 |
Day 5 - morning | 141 | 82.0 | 112 | 71.3 | 0.0107 |
Day 5 - evening | 156 | 90.7 | 127 | 80.9 | 0.0052 |
Children (5-12 years) | N=161 | N=158 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 0 | 0.0 | 0 | 0.0 | - |
Day 2 - morning | 9 | 5.6 | 7 | 4.4 | 0.31 |
Day 2 - evening | 14 | 8.7 | 11 | 7.0 | 0.28 |
Day 3 - morning | 25 | 15.5 | 17 | 10.8 | 0.01 |
Day 3 - evening | 52 | 32.3 | 35 | 22.2 | 0.02 |
Day 4 - morning | 72 | 44.7 | 55 | 34.8 | 0.03 |
Day 4 - evening | 87 | 54.0 | 67 | 42.4 | 0.01 |
Day 5 - morning | 111 | 68.9 | 87 | 55.1 | 0.005 |
Day 5 - evening | 120 | 74.5 | 100 | 63.3 | 0.01 |
Day 6 - morning | 139 | 86.3 | 115 | 72.8 | 0.001 |
Day 6 - evening | 148 | 91.9 | 123 | 77.8 | 0.001 |
Day 7 - morning | 152 | 94.4 | 135 | 85.4 | 0.003 |
Day 7 - evening | 159 | 98.8 | 141 | 89.2 | 0.001 |
Secondary endpoint: number and percentage of patients with persistent decrease of temperature <37°C (Efficacy Analysis)
Time Point | Active (Aviron Rapid) | Placebo | P-valuea | ||
n cumulative | % cumulative | n cumulative | % cumulative | ||
Adolescents (13-17 years) | N=172 | N=157 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 0 | 0.0 | 0 | 0.0 | - |
Day 2 - morning | 26 | 15.1 | 14 | 8.9 | 0.0427 |
Day 2 - evening | 38 | 22.1 | 22 | 14.0 | 0.0287 |
Day 3 - morning | 59 | 34.3 | 44 | 28.0 | 0.1092 |
Day 3 - evening | 82 | 47.7 | 60 | 38.2 | 0.0411 |
Day 4 - morning | 121 | 70.3 | 96 | 61.1 | 0.0393 |
Day 4 - evening | 136 | 79.1 | 107 | 68.2 | 0.0173 |
Day 5 - morning | 156 | 90.7 | 122 | 77.7 | <0.001 |
Day 5 - evening | 164 | 95.3 | 135 | 86.0 | 0.0017 |
Children (5-12 years) | N=161 | N=158 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 0 | 0.0 | 0 | 0.0 | - |
Day 2 - morning | 35 | 21.7 | 20 | 12.7 | 0.016 |
Day 2 - evening | 49 | 30.4 | 32 | 20.3 | 0.019 |
Day 3 - morning | 76 | 47.2 | 49 | 31.0 | 0.001 |
Day 3 - evening | 94 | 58.4 | 61 | 38.6 | 0.001 |
Day 4 - morning | 105 | 65.2 | 82 | 51.9 | 0.008 |
Day 4 - evening | 111 | 68.9 | 96 | 60.8 | 0.064 |
Day 5 - morning | 131 | 81.4 | 117 | 74.1 | 0.051 |
Day 5 - evening | 140 | 87.0 | 123 | 77.8 | 0.015 |
Day 6 - morning | 151 | 93.8 | 136 | 86.1 | 0.011 |
Day 6 - evening | 157 | 97.5 | 140 | 88.6 | 0.001 |
Day 7 - morning | 159 | 98.8 | 151 | 95.6 | 0.041 |
Day 7 - evening | 161 | 100.0 | 154 | 97.5 | 0.021 |
Secondary endpoint: number and percentage of patients taking antipyretics (Efficacy Analysis)
Time Point | Active (Aviron Rapid) | Placebo | P-valuea | ||
n cumulative | % cumulative | n cumulative | % cumulative | ||
Adolescents (13-17 years) | N=172 | N=157 | |||
Initial visit/Baseline | 172 | 100.0 | 157 | 100.0 | - |
Day 1 - evening | 134 | 77.9 | 135 | 86.0 | 0.0287 |
Day 2 - morning | 101 | 58.7 | 110 | 70.1 | 0.0156 |
Day 2 - evening | 101 | 58.7 | 103 | 65.6 | 0.0989 |
Day 3 - morning | 64 | 37.2 | 75 | 47.8 | 0.0259 |
Day 3 - evening | 49 | 28.5 | 62 | 39.5 | 0.0175 |
Day 4 - morning | 16 | 9.3 | 28 | 17.8 | 0.0175 |
Day 4 - evening | 12 | 7.0 | 19 | 12.1 | 0.0570 |
Day 5 - morning | 6 | 3.5 | 8 | 5.1 | 0.2365 |
Day 5 - evening | 2 | 1.2 | 6 | 3.8 | 0.0634 |
Children (5-12 years) | N=161 | N=158 | |||
Initial visit/Baseline | 161 | 100.0 | 158 | 100.0 | - |
Day 1 - evening | 126 | 78.3 | 132 | 83.5 | 0.230 |
Day 2 - morning | 97 | 60.2 | 107 | 67.7 | 0.165 |
Day 2 - evening | 84 | 52.2 | 99 | 62.7 | 0.058 |
Day 3 - morning | 53 | 32.9 | 77 | 48.7 | 0.004 |
Day 3 - evening | 47 | 29.2 | 75 | 47.5 | < 0.001 |
Day 4 - morning | 18 | 11.2 | 45 | 28.5 | < 0.001 |
Day 4 - evening | 15 | 9.3 | 46 | 29.1 | < 0.001 |
Day 5 - morning | 9 | 5.6 | 29 | 18.4 | < 0.001 |
Day 5 - evening | 3 | 1.9 | 22 | 13.9 | < 0.001 |
Day 6 - morning | 1 | 0.6 | 14 | 8.9 | < 0.001 |
Day 6 - evening | 0 | 0.0 | 14 | 8.9 | < 0.001 |
Day 7 - morning | 0 | 0.0 | 8 | 5.1 | 0.004 |
Day 7 - evening | 0 | 0.0 | 8 | 5.1 | 0.004 |
Secondary endpoint: mean total severity of clinical symptoms (Efficacy Analysis)
Time Point | Active (Aviron Rapid) | Placebo | P-valuea |
Adolescents (13-17 years) | N=172 | N=157 | |
Initial visit/Baseline | 25.6 | 24.9 | 0.515 |
Day 1 - evening | 25.4 | 26.0 | 0.625 |
Day 2 - morning | 22.4 | 23.8 | 0.238 |
Day 2 - evening | 20.0 | 21.5 | 0.215 |
Day 3 - morning | 14.6 | 17.2 | 0.017 |
Day 3 - evening | 12.6 | 14.8 | 0.041 |
Day 4 - morning | 9.3 | 10.6 | 0.149 |
Day 4 - evening | 7.3 | 8.5 | 0.159 |
Day 5 - morning | 5.3 | 6.2 | 0.171 |
Day 5 - evening | 3.6 | 4.8 | 0.071 |
Children (5-12 years) | N=161 | N=158 | |
Initial visit/Baseline | 24.6 | 23.5 | 0.304 |
Day 1 - evening | 25.4 | 24.0 | 0.239 |
Day 2 - morning | 22.0 | 21.4 | 0.655 |
Day 2 - evening | 20.1 | 19.6 | 0.663 |
Day 3 - morning | 16.5 | 16.6 | 0.93 |
Day 3 - evening | 14.6 | 15.8 | 0.271 |
Day 4 - morning | 11.4 | 13.2 | 0.077 |
Day 4 - evening | 10.0 | 11.7 | 0.094 |
Day 5 - morning | 7.5 | 9.2 | 0.034 |
Day 5 - evening | 6.9 | 7.8 | 0.233 |
Day 6 - morning | 5.3 | 6.8 | 0.028 |
Day 6 - evening | 4.3 | 5.4 | 0.07 |
Day 7 - morning | 3.1 | 4.2 | 0.034 |
Day 7 - evening | 2.2 | 3.4 | 0.009 |
Secondary endpoint: number and percentage of patients without nasal congestion (Efficacy Analysis)
Time Point | Active (Aviron Rapid) | Placebo | P-valuea | ||
n cumulative | % cumulative | n cumulative | % cumulative | ||
Adolescents (13-17 years) | N=160 | N=143 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 20 | 12.5 | 9 | 6.3 | 0.0335 |
Day 2 - morning | 22 | 13.8 | 12 | 8.4 | 0.0688 |
Day 2 - evening | 32 | 20.0 | 15 | 10.5 | 0.0113 |
Day 3 - morning | 44 | 27.5 | 24 | 16.8 | 0.0129 |
Day 3 - evening | 54 | 33.8 | 33 | 23.1 | 0.0200 |
Day 4 - morning | 74 | 46.3 | 55 | 38.5 | 0.0852 |
Day 4 - evening | 96 | 60.0 | 68 | 47.6 | 0.0153 |
Day 5 - morning | 120 | 75.0 | 90 | 62.9 | 0.0113 |
Day 5 - evening | 133 | 83.1 | 99 | 69.2 | 0.0022 |
Children (5-12 years) | N=148 | N=140 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 9 | 6.1 | 11 | 7.9 | 0.72 |
Day 2 - morning | 10 | 6.8 | 13 | 9.3 | 0.78 |
Day 2 - evening | 14 | 9.5 | 15 | 10.7 | 0.63 |
Day 3 - morning | 19 | 12.8 | 26 | 18.6 | 0.91 |
Day 3 - evening | 31 | 20.9 | 30 | 21.4 | 0.54 |
Day 4 - morning | 50 | 33.8 | 43 | 30.7 | 0.29 |
Day 4 - evening | 63 | 42.6 | 54 | 38.6 | 0.24 |
Day 5 - morning | 84 | 56.8 | 68 | 48.6 | 0.08 |
Day 5 - evening | 91 | 61.5 | 73 | 52.1 | 0.05 |
Day 6 - morning | 105 | 70.9 | 82 | 58.6 | 0.01 |
Day 6 - evening | 118 | 79.7 | 97 | 69.3 | 0.02 |
Day 7 - morning | 128 | 86.5 | 108 | 77.1 | 0.01 |
Day 7 - evening | 136 | 91.9 | 116 | 82.9 | 0.01 |
Secondary endpoint: number and percentage of patients without cough (Efficacy Analysis)
Time Point | Active (Aviron Rapid) | Placebo | P-valuea | ||
n cumulative | % cumulative | n cumulative | % cumulative | ||
Adolescents (13-17 years) | N=155 | N=142 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 24 | 15.5 | 14 | 9.9 | 0.0747 |
Day 2 - morning | 29 | 18.7 | 17 | 12.0 | 0.0555 |
Day 2 - evening | 37 | 23.9 | 20 | 14.1 | 0.0161 |
Day 3 - morning | 47 | 30.3 | 24 | 16.9 | 0.0034 |
Day 3 - evening | 54 | 34.8 | 32 | 22.5 | 0.0098 |
Day 4 - morning | 71 | 45.8 | 49 | 34.5 | 0.0237 |
Day 4 - evening | 83 | 53.5 | 65 | 45.8 | 0.0925 |
Day 5 - morning | 108 | 69.7 | 85 | 59.9 | 0.0385 |
Day 5 - evening | 123 | 79.4 | 102 | 71.8 | 0.0634 |
Children (5-12 years) | N=139 | N=142 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 5 | 3.6 | 5 | 3.5 | 0.48 |
Day 2 - morning | 6 | 4.3 | 10 | 7.0 | 0.83 |
Day 2 - evening | 10 | 7.2 | 12 | 8.5 | 0.65 |
Day 3 - morning | 11 | 7.9 | 17 | 12.0 | 0.87 |
Day 3 - evening | 19 | 13.7 | 22 | 15.5 | 0.66 |
Day 4 - morning | 34 | 24.5 | 35 | 24.6 | 0.51 |
Day 4 - evening | 42 | 30.2 | 46 | 32.4 | 0.65 |
Day 5 - morning | 59 | 42.4 | 58 | 40.8 | 0.39 |
Day 5 - evening | 68 | 48.9 | 66 | 46.5 | 0.34 |
Day 6 - morning | 83 | 59.7 | 73 | 51.4 | 0.08 |
Day 6 - evening | 98 | 70.5 | 85 | 59.9 | 0.03 |
Day 7 - morning | 113 | 81.3 | 101 | 71.1 | 0.02 |
Day 7 - evening | 124 | 89.2 | 111 | 78.2 | 0.01 |
Secondary endpoint: number and percentage of patients without sore throat (Efficacy Analysis)
Time Point | Active (Aviron Rapid) | Placebo | P-valuea | ||
n cumulative | % cumulative | n cumulative | % cumulative | ||
Adolescents (13-17 years) | N=164 | N=151 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 20 | 12.2 | 19 | 12.6 | 0.5429 |
Day 2 - morning | 31 | 18.9 | 28 | 18.5 | 0.4638 |
Day 2 - evening | 45 | 27.4 | 40 | 26.5 | 0.4287 |
Day 3 - morning | 67 | 40.9 | 49 | 32.5 | 0.0613 |
Day 3 - evening | 84 | 51.2 | 61 | 40.4 | 0.0273 |
Day 4 - morning | 119 | 72.6 | 92 | 60.9 | 0.0137 |
Day 4 - evening | 131 | 79.9 | 107 | 70.9 | 0.0316 |
Day 5 - morning | 143 | 87.2 | 127 | 84.1 | 0.2161 |
Day 5 - evening | 154 | 93.9 | 139 | 92.1 | 0.2653 |
Children (5-12 years) | N=129 | N=125 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 15 | 11.6 | 15 | 12.0 | 0.54 |
Day 2 - morning | 23 | 17.8 | 21 | 16.8 | 0.42 |
Day 2 - evening | 32 | 24.8 | 26 | 20.8 | 0.22 |
Day 3 - morning | 50 | 38.8 | 46 | 36.8 | 0.37 |
Day 3 - evening | 64 | 49.6 | 57 | 45.6 | 0.26 |
Day 4 - morning | 85 | 65.9 | 68 | 54.4 | 0.03 |
Day 4 - evening | 98 | 76.0 | 79 | 63.2 | 0.01 |
Day 5 - morning | 107 | 82.9 | 89 | 71.2 | 0.01 |
Day 5 - evening | 113 | 87.6 | 98 | 78.4 | 0.02 |
Day 6 - morning | 121 | 93.8 | 109 | 87.2 | 0.03 |
Day 6 - evening | 122 | 94.6 | 114 | 91.2 | 0.14 |
Day 7 - morning | 127 | 98.4 | 118 | 94.4 | 0.04 |
Day 7 - evening | 128 | 99.2 | 122 | 97.6 | 0.15 |
Secondary endpoint: number and percentage of patients without headache (Efficacy Analysis)
Time Point | Active (Aviron Rapid) | Placebo | P-valuea | ||
n cumulative | % cumulative | n cumulative | % cumulative | ||
Adolescents (13-17 years) | N=163 | N=143 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 23 | 14.1 | 22 | 15.4 | 0.6256 |
Day 2 - morning | 41 | 25.2 | 36 | 25.2 | 0.5000 |
Day 2 - evening | 61 | 37.4 | 46 | 32.2 | 0.1706 |
Day 3 - morning | 96 | 58.9 | 77 | 53.8 | 0.1846 |
Day 3 - evening | 112 | 68.7 | 91 | 63.6 | 0.1732 |
Day 4 - morning | 130 | 79.8 | 111 | 77.6 | 0.3193 |
Day 4 - evening | 142 | 87.1 | 119 | 83.2 | 0.1684 |
Day 5 - morning | 151 | 92.6 | 132 | 92.3 | 0.4605 |
Day 5 - evening | 158 | 96.9 | 135 | 94.4 | 0.1402 |
Children (5-12 years) | N=122 | N=129 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 13 | 10.7 | 19 | 14.7 | 0.82 |
Day 2 - morning | 35 | 28.7 | 40 | 31.0 | 0.65 |
Day 2 - evening | 52 | 42.6 | 55 | 42.6 | 0.5 |
Day 3 - morning | 74 | 60.7 | 73 | 56.6 | 0.25 |
Day 3 - evening | 83 | 68.0 | 83 | 64.3 | 0.26 |
Day 4 - morning | 98 | 80.3 | 96 | 74.4 | 0.13 |
Day 4 - evening | 104 | 85.2 | 103 | 79.8 | 0.13 |
Day 5 - morning | 112 | 91.8 | 116 | 89.9 | 0.3 |
Day 5 - evening | 113 | 92.6 | 118 | 91.5 | 0.37 |
Day 6 - morning | 117 | 95.9 | 120 | 93.0 | 0.15 |
Day 6 - evening | 120 | 98.4 | 121 | 93.8 | 0.03 |
Day 7 - morning | 122 | 100.0 | 124 | 96.1 | 0.01 |
Day 7 - evening | 122 | 100.0 | 126 | 97.7 | 0.04 |
Secondary endpoint: number and percentage of patients without fatigue (Efficacy Analysis)
Time Point | Active (Aviron Rapid) | Placebo | P-valuea | ||
n cumulative | % cumulative | n cumulative | % cumulative | ||
Adolescents (13-17 years) | N=164 | N=149 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 20 | 8.5 | 17 | 8.7 | 0.5251 |
Day 2 - morning | 44 | 18.3 | 34 | 21.5 | 0.7609 |
Day 2 - evening | 61 | 28.0 | 58 | 27.5 | 0.4607 |
Day 3 - morning | 96 | 46.3 | 98 | 47.7 | 0.5979 |
Day 3 - evening | 136 | 59.8 | 143 | 55.0 | 0.1955 |
Day 4 - morning | 190 | 76.2 | 196 | 73.2 | 0.2708 |
Day 4 - evening | 228 | 84.1 | 225 | 81.9 | 0.3022 |
Day 5 - morning | 265 | 93.3 | 257 | 89.3 | 0.1038 |
Day 5 - evening | 282 | 94.5 | 275 | 93.3 | 0.3285 |
Children (5-12 years) | N=145 | N=139 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 12 | 8.3 | 8 | 5.8 | 0.21 |
Day 2 - morning | 31 | 21.4 | 23 | 16.5 | 0.14 |
Day 2 - evening | 49 | 33.8 | 36 | 25.9 | 0.07 |
Day 3 - morning | 79 | 54.5 | 61 | 43.9 | 0.03 |
Day 3 - evening | 90 | 62.1 | 70 | 50.4 | 0.02 |
Day 4 - morning | 112 | 77.2 | 92 | 66.2 | 0.02 |
Day 4 - evening | 119 | 82.1 | 99 | 71.2 | 0.01 |
Day 5 - morning | 128 | 88.3 | 113 | 81.3 | 0.04 |
Day 5 - evening | 131 | 90.3 | 121 | 87.1 | 0.19 |
Day 6 - morning | 138 | 95.2 | 126 | 90.6 | 0.06 |
Day 6 - evening | 140 | 96.6 | 131 | 94.2 | 0.16 |
Day 7 - morning | 142 | 97.9 | 133 | 95.7 | 0.14 |
Day 7 - evening | 144 | 99.3 | 135 | 97.1 | 0.08 |
Secondary endpoint: number and percentage of patients without sleep disturbance (Efficacy Analysis)
Time Point | Active (Aviron Rapid) | Placebo | P-valuea | ||
n cumulative | % cumulative | n cumulative | % cumulative | ||
Adolescents (13-17 years) | N=114 | N=108 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 39 | 34.2 | 32 | 29.6 | 0.2313 |
Day 2 - morning | 51 | 44.7 | 42 | 38.9 | 0.1907 |
Day 2 - evening | 65 | 57.0 | 58 | 53.7 | 0.3105 |
Day 3 - morning | 83 | 72.8 | 69 | 63.9 | 0.0769 |
Day 3 - evening | 88 | 77.2 | 75 | 69.4 | 0.0943 |
Day 4 - morning | 101 | 88.6 | 84 | 77.8 | 0.0154 |
Day 4 - evening | 103 | 90.4 | 89 | 82.4 | 0.0406 |
Day 5 - morning | 107 | 93.9 | 97 | 89.8 | 0.1315 |
Day 5 - evening | 110 | 96.5 | 102 | 94.4 | 0.2258 |
Children (5-12 years) | N=109 | N=89 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 8 | 7.3 | 6 | 6.7 | 0.43 |
Day 2 - morning | 29 | 26.6 | 23 | 25.8 | 0.44 |
Day 2 - evening | 46 | 42.2 | 35 | 39.3 | 0.33 |
Day 3 - morning | 63 | 57.8 | 42 | 47.2 | 0.06 |
Day 3 - evening | 72 | 66.1 | 47 | 52.8 | 0.02 |
Day 4 - morning | 82 | 75.2 | 57 | 64.0 | 0.04 |
Day 4 - evening | 91 | 83.5 | 70 | 78.7 | 0.19 |
Day 5 - morning | 95 | 87.2 | 74 | 83.1 | 0.21 |
Day 5 - evening | 97 | 89.0 | 76 | 85.4 | 0.22 |
Day 6 - morning | 102 | 93.6 | 80 | 89.9 | 0.17 |
Day 6 - evening | 107 | 98.2 | 83 | 93.3 | 0.04 |
Day 7 - morning | 108 | 99.1 | 84 | 94.4 | 0.02 |
Day 7 - evening | 109 | 100.0 | 86 | 96.6 | 0.02 |
Secondary endpoint: number and percentage of patients considered fully recovered (Efficacy Analysis)
Time Point | Active (Aviron Rapid) | Placebo | P-valuea | ||
n cumulative | % cumulative | n cumulative | % cumulative | ||
Adolescents (13-17 years) | N=172 | N=157 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 0 | 0.0 | 0 | 0.0 | - |
Day 2 - morning | 55 | 32.0 | 32 | 20.4 | 0.0086 |
Day 2 - evening | 107 | 62.2 | 71 | 45.2 | 0.0010 |
Day 3 - morning | 125 | 72.7 | 95 | 60.5 | 0.0094 |
Day 3 - evening | 148 | 86.0 | 131 | 83.4 | 0.2561 |
Day 4 - morning | 162 | 94.2 | 141 | 89.8 | 0.0697 |
Day 4 - evening | 168 | 97.7 | 151 | 96.2 | 0.2134 |
Day 5 - morning | 171 | 99.4 | 155 | 98.7 | 0.2549 |
Day 5 - evening | 172 | 100.0 | 157 | 100.0 | - |
Day 6 – morning (closing visit) | 172 | 100.0 | 157 | 100.0 | - |
Children (5-12 years) | N=161 | N=158 | |||
Initial visit/Baseline | 0 | 0.0 | 0 | 0.0 | - |
Day 1 - evening | 31 | 19.3 | 27 | 17.1 | 0.305 |
Day 2 - morning | 50 | 31.1 | 42 | 26.6 | 0.187 |
Day 2 - evening | 82 | 50.9 | 66 | 41.8 | 0.051 |
Day 3 - morning | 100 | 62.1 | 81 | 51.3 | 0.025 |
Day 3 - evening | 124 | 77.0 | 104 | 65.8 | 0.013 |
Day 4 - morning | 134 | 83.2 | 117 | 74.1 | 0.023 |
Day 4 - evening | 143 | 88.8 | 130 | 82.3 | 0.049 |
Day 5 - morning | 149 | 92.5 | 140 | 88.6 | 0.116 |
Day 5 - evening | 156 | 96.9 | 145 | 91.8 | 0.024 |
Day 6 - morning | 159 | 98.8 | 151 | 95.6 | 0.041 |
Day 6 - evening | 161 | 100.0 | 156 | 98.7 | 0.073 |
Day 7 - morning | 161 | 100.0 | 157 | 99.4 | 0.162 |
Day 7 - evening | 161 | 100.0 | 158 | 100.0 | - |
Day 8 – morning (closing visit) | 161 | 100.0 | 158 | 100.0 | - |