Clinical Trial Results:
Double-blind, randomised, placebo-controlled study evaluating the efficacy and safety of Tavipec capsules in acute Bronchitis
A prospective, multi-centre, parallel group, interventional clinical phase IV study
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Summary
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EudraCT number |
2013-004836-31 |
Trial protocol |
AT |
Global end of trial date |
04 Jan 2016
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Results information
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Results version number |
v1(current) |
This version publication date |
31 Jul 2022
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First version publication date |
31 Jul 2022
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Other versions |
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Summary report(s) |
Double-blind, randomized, placebo-controlled study evaluating the Efficacy and Safety of Tavipec® capsules in acute Bronchitis |
Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
TAV01/13
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Additional study identifiers
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ISRCTN number |
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US NCT number |
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WHO universal trial number (UTN) |
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Sponsors
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Sponsor organisation name |
Pharmazeutische Fabrik Montavit Ges.m.b.H.
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Sponsor organisation address |
Salzbergstraße 96, Absam, Austria, 6067
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Public contact |
Mag. Gabriele Zacke, Clinical Trial Department, 0043 0522357926234, gabriele.zacke@montavit.com
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Scientific contact |
Mag. Gabriele Zacke, Clinical Trial Department, 0043 0522357926234, gabriele.zacke@montavit.com
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Final
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Date of interim/final analysis |
04 Jan 2016
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
04 Jan 2016
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Global end of trial reached? |
Yes
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Global end of trial date |
04 Jan 2016
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective was the mean difference of a defined total bronchitis severity score (BSS) of 25 % between the verum group and the placebo group after 7 days of full medication dose.
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Protection of trial subjects |
Acute bronchitis generally is a self-limiting disease and care for acute bronchitis is primarily supportive and aims on alleviation of symptoms.
Therefore, no problems of ethics, acceptability, and feasibility are assumed to arise from the use of a placebo-concurrent control group.
Moreover, whith the selected inclusion criteria a safety net was broadly spanned to ensure that severe cases of bronchitis requiring antibiotic treatment would be excluded.
Nevertheless, a close monitoring of patients was done. After baseline next evaluation was performed following seven days of treatment, so the detection of a possible worsening of the clinical condition has been guaranteed. In case of treatment failure at this time point, treatment would have been discontinued. Patients were advised about re-consulting at any time during the study if there was a significant worsening of symptoms or occurrence of complications, including a rise in temperature above 39 °C.
For safety reasons, these subjects would have been deemed clinical failures and promptly scheduled for a treatment failure visit.
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Background therapy |
Apart from saline inhalation no other concomitant medications were allowed for relief of bronchitis symptoms. | ||
Evidence for comparator |
Tavipec is a herbal medicinal product containing spicae aetheroleum, an essential oil gained from the sun-dried flowers of Lavendula spica L., as the active ingredient. Its main constituents are linalool, 1,8-cineole (synonym: eucalyptol) and camphor. Tavipec acts secretolytic and promotes expectoration. It positively influences mucociliary clearance and increases phagozytosis capacity, resulting in an increase of unspecific immunity. Tavipec is authorised in twelve countries world-wide (i.e., Austria, Albania, Bulgaria, Georgia, Iran, Kazakhstan, Kyrgyztan, Modlova, Romania, Thailand, Ukraine and Uzbekistan). The first marketing autorisation was obtained in Austria on February 25, 1959. The experience gained from September 25, 2009 - September 25, 2010, the period which was covered by the Periodic Safety Update Report (PSUR), confirms the established safety profile of Tavipec capsules during this observation period. According to the summary of product characteristics (SmPC) and package insert (PI), Tavipec is a herbal drug to support specific measures in rhinosinusitis or cough associated with a cold. The present placebo-controlled clinical study was done to extend information on efficacy and safety of Tavipec capsules in patients suffering from acute bronchitis. | ||
Actual start date of recruitment |
03 Feb 2014
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Long term follow-up planned |
No
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Independent data monitoring committee (IDMC) involvement? |
No
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Austria: 23
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Country: Number of subjects enrolled |
Poland: 235
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Worldwide total number of subjects |
258
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EEA total number of subjects |
258
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
243
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From 65 to 84 years |
15
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85 years and over |
0
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Recruitment
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Recruitment details |
Patients were recruited between May 2014 and January 2016 in 3 study centers in Austria and 5 study centers in Poland by general practitioner, specialist of pneumology or by hospital doctors from pneumology clinics. | ||||||||||||||||||||||||||||||||||||||||||
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Pre-assignment
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Screening details |
There was no screening period as it was an acute treatment. Only patients suffering from uncomplicated acute bronchitis with onset of first symptoms within two days before start of treatment were recruited. In summary, 269 patients were assessed for eligibility of which 8 patient were excluded after inclusion (n=258). | ||||||||||||||||||||||||||||||||||||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | ||||||||||||||||||||||||||||||||||||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | ||||||||||||||||||||||||||||||||||||||||||
Roles blinded |
Subject, Investigator | ||||||||||||||||||||||||||||||||||||||||||
Blinding implementation details |
Each patient received a medication bottle with capsules. In the placebo group the bottles contain Placebo, identical in appearance &taste to verum, being indistinguishable from their respective active investigational drug. Randomisation list was compiled by Sponsor. Packaging and labelling was performed by Sponsor in accordance to Sponsor's SOP. PI received a sealed emergeny envelope for each subject. Each envelope contains the identity of a subject's treatment. Opening was documented in CRF.
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | ||||||||||||||||||||||||||||||||||||||||||
Arm description |
The objective of the study was to evaluate the efficacy and safety of Tavipec® as compared to placebo in patients suffering from acute Bronchitis. Acute bronchitis generally is a self-limiting disease and care for acute bronchitis is primarily supportive and aims on alleviation of symptoms. Therefore, no problems of ethics, acceptability, and feasibility are assumed to arise from the use of a placebo-concurrent control group. Oral intake of two Placebo capsules three times daily for ten days of treatment. | ||||||||||||||||||||||||||||||||||||||||||
Arm type |
Placebo | ||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Placebo
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Placebo in form of capsules with gastroresistant coating filled with Medium-Chain Triglycerides (Manufacturer: Pharmazeutische Fabrik Montavit Ges.m.b.H).
The route for all study medications was oral application. Placebo capsules was ingested three times daily (Morning: 2 capsules; Lunchtime: 2 capsules; Evening: 2 capsules)
Patients were instructed to swallow capsules as a whole with some liquid, 30 minutes before a meal.
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Arm title
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Tavipec | ||||||||||||||||||||||||||||||||||||||||||
Arm description |
The objective of the study was to evaluate the efficacy and safety of Tavipec® as compared to placebo in patients suffering from acute Bronchitis. Oral intake of two Tavipec capsules three times daily for ten days of treatment. | ||||||||||||||||||||||||||||||||||||||||||
Arm type |
Active comparator | ||||||||||||||||||||||||||||||||||||||||||
Investigational medicinal product name |
Tavipec®
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Capsule
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Routes of administration |
Oral use
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Dosage and administration details |
Tavipec® are capsules with gastroresistant coating containing 10 mg spicae aetheroleum.
The route for all study medications was oral application.
The study medication was provided for the investigators by Pharmazeutische Fabrik Montavit Ges.m.b.H., Austria.
Tavipec was ingested three times daily (Morining: 2 capsules; Lunchtime: 2 capsules; Evening: 2 capsules).
Patients were instructed to swallow capsules as a whole with some liquid, 30 minutes before a meal.
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Baseline characteristics reporting groups
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Reporting group title |
Overall trial
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Reporting group description |
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Subject analysis sets
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Subject analysis set title |
Placebo group
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||
Subject analysis set description |
Analysis of Placebo group
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Subject analysis set title |
Tavipec group
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Subject analysis set type |
Full analysis | |||||||||||||||||||||||||||||||||
Subject analysis set description |
Analysis of Tavipec group
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
The objective of the study was to evaluate the efficacy and safety of Tavipec® as compared to placebo in patients suffering from acute Bronchitis. Acute bronchitis generally is a self-limiting disease and care for acute bronchitis is primarily supportive and aims on alleviation of symptoms. Therefore, no problems of ethics, acceptability, and feasibility are assumed to arise from the use of a placebo-concurrent control group. Oral intake of two Placebo capsules three times daily for ten days of treatment. | ||
Reporting group title |
Tavipec
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Reporting group description |
The objective of the study was to evaluate the efficacy and safety of Tavipec® as compared to placebo in patients suffering from acute Bronchitis. Oral intake of two Tavipec capsules three times daily for ten days of treatment. | ||
Subject analysis set title |
Placebo group
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Analysis of Placebo group
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Subject analysis set title |
Tavipec group
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Subject analysis set type |
Full analysis | ||
Subject analysis set description |
Analysis of Tavipec group
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End point title |
PRIMARY EFFICACY EVALUATION BSS: Mean change (improvement from baseline) at day 7, ITT/PP | ||||||||||||
End point description |
As the only primary efficacy parameter the mean difference of a defined total BSS of 25 % between the verum group and the placebo group after 7 days of full medication dose was chosen.
A sum score from signs and symptoms was formed for evaluation purposes, comparing changes from baseline in both treatment groups.
The BSS in the presented study is the sum of the indivual scores of: Cough, Sputum, Rales/rhonchi, Chest pain during coughing and Dyspnea (0= absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe)
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End point type |
Primary
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End point timeframe |
Primary end point was assessed between May 2014 and January 2016
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Attachments |
Tav01-13_Results_primary endpoint |
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| Notes [1] - ITT Placebo group used for analysis [2] - ITT Tavipec group used for analysis |
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Statistical analysis title |
Primary endpoint: BSS difference day 0 and 7 (ITT) | ||||||||||||
Statistical analysis description |
The main efficacy variable is quantitative, however, not necessarily normally distributed;
Therefore a two sided (α = 5 %) Mann-Whitney test (rank-sum test) was applied to test the following hypothesis (null hypothesis):
H0: μ BSS (day 7) placebo = μ BSS (day 7) verum
H1: μ BSS (day 7) placebo ≠ μ BSS (day 7) verum
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Comparison groups |
Placebo group v Tavipec group
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Number of subjects included in analysis |
245
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Confidence interval |
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sides |
2-sided
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lower limit |
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upper limit |
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Variability estimate |
Standard deviation
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End point title |
SECONDARY EFFICACY EVALUATION BSS: Mean change (improvement from baseline) at day 10, PP | ||||||||||||
End point description |
As an second efficacy parameter the mean difference of a defined total BSS of 25 % between the verum group and the placebo group after 10 days of full medication dose was chosen.
A sum score from signs and symptoms was formed for evaluation purposes, comparing changes from baseline in both treatment groups.
The BSS in the presented study is the sum of the indivual scores of: Cough, Sputum, Rales/rhonchi, Chest pain during coughing and Dyspnea (0= absent, 1 = mild, 2 = moderate, 3 = severe, 4 = very severe)
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End point type |
Secondary
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End point timeframe |
May 2014 - January 2016
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Attachments |
Tav01-13_Secondary endpoints_results |
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| Notes [3] - PP Placebo group used for analysis [4] - PP Tavipec group used for analysis |
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Statistical analysis title |
Secondary endpoint: BSS difference day 0 & 10 (PP) | ||||||||||||
Statistical analysis description |
The main efficacy variable is quantitative, however, not necessarily normally distributed;
Therefore a two sided (α = 5 %) Mann-Whitney test (rank-sum test) was applied to test the following hypothesis (null hypothesis):
H0: μ BSS (day 7) placebo = μ BSS (day 7) verum
H1: μ BSS (day 7) placebo ≠ μ BSS (day 7) verum
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Comparison groups |
Placebo group v Tavipec group
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Number of subjects included in analysis |
229
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Analysis specification |
Pre-specified
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Analysis type |
superiority | ||||||||||||
P-value |
< 0.05 | ||||||||||||
Method |
Wilcoxon (Mann-Whitney) | ||||||||||||
Parameter type |
Mean difference (final values) | ||||||||||||
Confidence interval |
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level |
95% | ||||||||||||
sides |
2-sided
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lower limit |
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upper limit |
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Variability estimate |
Standard deviation
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End point title |
SECONDARY EFFICACY QoL score: Mean change (improvement from baseline) at day 7 and day 10, ITT | ||||||||||||
End point description |
The impact of the disease on quality of life was evaluated globally by the question "How troublesome are your symptoms of bronchitis". At any visit, patients had to assess their condition on a 10-point scoring system ranging from "Not troublesome" (= 0) to "Worst thinkable troublesome" (= 10).
Results below show mean change at day 10 for ITT (QoL) Placebo and Tavipec group (n = 112 / n = 119).
Summary of all QoL results (baseline, day 7 and day 10) shown in the attachment.
Number of patients of ITT Placebo group (day 7) = 120
Number of patients of ITT Tavipec group (day 7) = 125
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End point type |
Secondary
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End point timeframe |
May 2014 - January 2016
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Attachments |
Tav01-13_Secondary endpoints_results |
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| Notes [5] - ITT (QoL) Placebo group for d 10 [6] - ITT (QoL) Tavipec group for d 10 |
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| No statistical analyses for this end point | |||||||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Non-serious AEs assessed by the investigator have to be reported to Montavit by e-mail within 30 days from receipt.
All SAEs have to be reported at latest within 24 hours of the first awareness of the event.
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Adverse event reporting additional description |
At each visit, all AEs either reported by the patient or observed by the investigator were evaluated and recorded into the CRF. Each AE was described by its duration, frequency, severity, its relationship to the trial medication, its influence on administration or study medication and a possible requirement of therapy.
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Assessment type |
Systematic | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
MedDRA | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
17.1
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Reporting groups
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Reporting group title |
Tavipec® capsules
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Reporting group description |
Tavipec® capsules with gastroresistant coating; 2 capsules containing 150 mg spicae aetheroleum each, thrice daily | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
Placebo capsules with gastroresistant coating; 2 capsules containing Medium-Chain Triglycerides each, thrice daily | |||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| n.a | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/29209859 |
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