ClinicalTrials.gov
ClinicalTrials.gov Menu

Comparison of Efficacy and Tolerability of Two Cough Syrups in Cough Due to Cold in Children. (URTI)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT01968434
Recruitment Status : Completed
First Posted : October 24, 2013
Results First Posted : November 2, 2015
Last Update Posted : February 23, 2018
Sponsor:
Collaborator:
Aboca Spa Societa' Agricola
Information provided by (Responsible Party):
Avner Herman Cohen, Clalit Health Services

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Outcomes Assessor);   Primary Purpose: Treatment
Conditions Cough
Upper Respiratory Tract Infection
Interventions Device: protective cough syrup
Drug: carbocisteine cough syrup
Enrollment 150
Recruitment Details Recruiting took place within the Clalit health service community day hospitals. Community day hospitals are places where parents go for usual illnesses and treat most community ailments.
Pre-assignment Details Access for eligibility= 195 Excluded =45 (refused to participate n= 24, not meeting inclusion criteria n=21)
Arm/Group Title Protective Cough Syrup Carbocisteine Cough Syrup
Hide Arm/Group Description

syrup containing honey, plantago lanceolata, grindelia robusta, helichrysum italicum ina syrup form. The cough syrup is a CE marked medical device acting in a non pharmacological way to reduce cough.

Dosage: 6,5 ml three times a day for the duration of the study (4 nights, 3 days)

protective cough syrup: The mucoadhesive and radical scavenging properties of the components create a protective film on the pharynx which protects irritated mucosa from cough generating stimuli such as post nasal drip, irritating elements, dehydration.

Access for eligibility= 195 Excluded =45 (refused to participate n= 24, not meeting inclusion criteria n=21) Enrolled: 150 completed pre-treatment questionnaire and randomized into groups Allocated protective syrup n = 78 received intervention n= 78 Lost to follow up n=3 Discontinued intervention n=0 Analyzed n=75 Excluded from analysis n=0

Dosage 20-25 mg/kg/day three times a day (3 days/4 nights)

carbocisteine cough syrup: Mucolytic

Access for eligibility= 195 Excluded =45 (refused to participate n= 24, not meeting inclusion criteria n=21) Enrolled: 150 completed pre-treatment questionnaire and randomized into groups Allocated carbocisteine syrup n = 72 received intervention n= 72 Lost to follow up n=6 Discontinued intervention n=0 Analyzed n=66 Excluded from analysis n=0

Period Title: Overall Study
Started 78 72
Completed 75 66
Not Completed 3 6
Reason Not Completed
Lost to Follow-up             3             6
Arm/Group Title Protective Cough Syrup Carbocisteine Cough Syrup Total
Hide Arm/Group Description

syrup containing honey, plantago lanceolata, grindelia robusta, helichrysum italicum in a syrup form. The cough syrup is a CE marked medical device acting in a non pharmacological way to reduce cough.

Dosage: 6.5 ml three times a day for the duration of the study (4 nights, 3 days)

protective cough syrup: The mucoadhesive and radical scavenging properties of the components create a protective film on the pharynx which protects irritated mucosa from cough generating stimuli such as post nasal drip, irritating elements, dehydration.

Enrolled: 150 completed pre-treatment questionnaire and randomized into groups Allocated protective syrup n = 78 received intervention n= 78 Lost to follow up n=3 Discontinued intervention n=0 Analyzed n=75 Excluded from analysis n=0

Dosage 20-25 mg/kg/day three times a day (3 days/4 nights)

carbocisteine cough syrup: Mucolytic

Enrolled: 150 completed pre-treatment questionnaire and randomized into groups Allocated carbocisteine syrup n = 72 received intervention n= 72 Lost to follow up n=6 Discontinued intervention n=0 Analyzed n=66 Excluded from analysis n=0

Total of all reporting groups
Overall Number of Baseline Participants 78 72 150
Hide Baseline Analysis Population Description
Enrolled patients had a minimum cough intensity both day and night, according to questionnaire, had not received any cough medicine the day before enrollment and fulfilled all inclusion criteria.
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Months
Number Analyzed 78 participants 72 participants 150 participants
42.49  (12.96) 43.17  (14.57) 42.8  (13.7)
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 78 participants 72 participants 150 participants
Female
41
  52.6%
38
  52.8%
79
  52.7%
Male
37
  47.4%
34
  47.2%
71
  47.3%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
Israel Number Analyzed 78 participants 72 participants 150 participants
78 72 150
Participants coughing since ≥ 3 days at time of enrollment  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 78 participants 72 participants 150 participants
47 46 93
1.Primary Outcome
Title Change in Night Cough Score on First Night of Treatment (From N0 to N1)
Hide Description Night cough is most bothersome to the child and family. Cough was measured with a validated questionnaire which asks parents to rate 5 aspects of night cough: frequency, severity, bothersomeness, child sleep and parent sleep according to a 7 point Likert scale, from 0 (not at all) to 6 (extremely). Lower scores indicate a better condition. The morning after the first night of treatment (N1) the parents rated the passed night by scoring from 0-6 each of the 5 aspects of night cough. The sum of scores for all 5 aspects gives the combined night cough score. This score, ranging between 0-30, was subtracted from the sum of all aspects, also ranging between 0-30, form the basal night cough score of the night before enrollment (N0). This change is recorded as "change in combined night cough score" and it refers to the change from N0 to N1. Negative values of the change indicate an improvement in the condition of the patient.
Time Frame 1 night from before enrollment (N0) to first night after treatment (N1)
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
the population analyzed are the children who completed the protocol and submitted the complete questionnaire for night and day cough. 78 patients were enrolled in the protective syrup Group and 72 in the carbocysteine Group. 3 patients in the protective syrup group and 6 in the carbocysteine group never began the study.
Arm/Group Title Protective Cough Syrup Carbocisteine Cough Syrup
Hide Arm/Group Description:

syrup containing honey, plantago lanceolata, grindelia robusta, helichrysum italicum ina syrup form. The cough syrup is a CE marked medical device acting in a non pharmacological way to reduce cough.

Dosage: 20 ml divided in three doses per day for the duration of the study (4 nights, 3 days)

protective cough syrup: The mucoadhesive and radical scavenging properties of the components create a protective film on the pharynx which protects irritated mucosa from cough generating stimuli such as post nasal drip, irritating elements, dehydration.

Dosage 20-25 mg/kg/day three times a day (3 days/4 nights)

carbocisteine cough syrup: Mucolytic

Overall Number of Participants Analyzed 75 66
Mean (Standard Error)
Unit of Measure: change in combined night cough score
-5.16  (0.85) -1.77  (0.67)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Protective Cough Syrup, Carbocisteine Cough Syrup
Comments The sample size was calculated to detect a 0.75 point difference between any two treatment groups with a 90% power and p<0.05. Such sample size was 60 subject which was elevated ot 75 subjects per group to account for drop outs. For comparison of cough evaluation before and after treatment a paired Student t test was used.
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
2.Secondary Outcome
Title Change in Night Cough Score at End of Study (From N0 to N4)
Hide Description A validated cough questionnaire measuring 5 aspects of night cough (frequency, severity, bothersomeness, child sleep and parents' sleep) on a 7 point Likert scale was used each morning to rate the passed night. The scale rates each parameter from 0 (not at all) to 6 (extremely). Every night of the trial is rated. The morning after the last night of the study (N4) the parents rated the passed night by scoring from 0-6 each of the 5 aspects of night cough. The summed score for all aspects gives the combined night cough score. This score, ranging between 0-30, was subtracted from the sum of all aspects, also ranging between 0-30, form the basal night cough score of the night before enrollment (N0). This change is recorded as "change in combined night cough score" and it refers to the change from N0 to N4. Negative values of the change indicate an improvement in the condition of the patient.
Time Frame 4 nights (onset of trial Night 1 to Night 4) and 3 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
78 patients were enrolled in the protective syrup Group and 72 in the carbocysteine Group. 3 patients in the protective syrup group and 6 in the carbocysteine group never began the study. 7 patients from the protective syrup group and twelve 12 patients from the carbocysteine group did not answer the questions for the last night.
Arm/Group Title Protective Cough Syrup Carbocisteine Cough Syrup
Hide Arm/Group Description:

syrup containing honey, plantago lanceolata, grindelia robusta, helichrysum italicum ina syrup form. The cough syrup is a CE marked medical device acting in a non pharmacological way to reduce cough.

Dosage: 20 ml divided in three doses per day for the duration of the study (4 nights, 3 days)

protective cough syrup: The mucoadhesive and radical scavenging properties of the components create a protective film on the pharynx which protects irritated mucosa from cough generating stimuli such as post nasal drip, irritating elements, dehydration.

Dosage 20-25 mg/kg/day three times a day (3 days/4 nights)

carbocisteine cough syrup: Mucolytic

Overall Number of Participants Analyzed 71 60
Mean (Standard Error)
Unit of Measure: change in combined night cough score
-13.92  (0.92) -9.48  (1.08)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Protective Cough Syrup, Carbocisteine Cough Syrup
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.01
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
3.Secondary Outcome
Title Change in Day Cough Score at End of Study (From D0 to D4)
Hide Description A validated cough questionnaire measuring 3 aspects of daytime cough (frequency, severity, bothersomeness) on a 7 point Likert scale was used each evening to rate the passed day, as regards these aspects. The scale rates each parameter from 0 (not at all) to 6 (extremely). Every day of the trial is rated. The last evening of the study (D4) the parents rated the passed day by scoring from 0-6 each of the 3 aspects of day cough. The summed score for all aspects gives the combined day cough score. This score, ranging between 0-18, was subtracted from the sum of all aspects, also ranging between 0-18, form the basal day cough score of the day before enrollment (D0). This change is recorded as "change in combined day cough score" and it refers to the change from D0 to D4. Negative values of the change indicate an improvement in the condition of the patient.
Time Frame 4 nights (onset of trial Night 1 to Night 4) and 3 days
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
78 patients were enrolled in the protective syrup Group and 72 in the carbocysteine Group. 3 patients in the protective syrup group and 6 in the carbocysteine group never began the study. 6 patients from the protective syrup group and twelve 11 patients from the carbocysteine group did not answer the questions for the last day.
Arm/Group Title Protective Cough Syrup Carbocisteine Cough Syrup
Hide Arm/Group Description:

syrup containing honey, plantago lanceolata, grindelia robusta, helichrysum italicum ina syrup form. The cough syrup is a CE marked medical device acting in a non pharmacological way to reduce cough.

Dosage: 20 ml divided in three doses per day for the duration of the study (4 nights, 3 days)

protective cough syrup: The mucoadhesive and radical scavenging properties of the components create a protective film on the pharynx which protects irritated mucosa from cough generating stimuli such as post nasal drip, irritating elements, dehydration.

Dosage 20-25 mg/kg/day three times a day (3 days/4 nights)

carbocisteine cough syrup: Mucolytic

Overall Number of Participants Analyzed 72 61
Mean (Standard Error)
Unit of Measure: change in combined day cough score
-6.17  (0.43) -4.54  (0.6)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Protective Cough Syrup, Carbocisteine Cough Syrup
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value <0.05
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Time Frame Adverse events were recorded during study period, from first enrollment to last collected data, which was a period of 5 months. Due to the nature of ailment and of treatment it was envisaged that any adverse event would be evident within study period.
Adverse Event Reporting Description Adverse events were systematically collected by the CRF questionnaire.
 
Arm/Group Title Protective Cough Syrup Carbocisteine Cough Syrup
Hide Arm/Group Description

syrup containing honey, plantago lanceolata, grindelia robusta, helichrysum italicum ina syrup form. The cough syrup is a CE marked medical device acting in a non pharmacological way to reduce cough.

Dosage: 6,5 ml three times a day for the duration of the study (4 nights, 3 days)

protective cough syrup: The mucoadhesive and radical scavenging properties of the components create a protective film on the pharynx which protects irritated mucosa from cough generating stimuli such as post nasal drip, irritating elements, dehydration.

Dosage 20-25 mg/kg/day three times a day (3 days/4 nights)

carbocisteine cough syrup: Mucolytic

All-Cause Mortality
Protective Cough Syrup Carbocisteine Cough Syrup
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
Protective Cough Syrup Carbocisteine Cough Syrup
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   0/75 (0.00%)      0/66 (0.00%)    
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
Protective Cough Syrup Carbocisteine Cough Syrup
Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   6/75 (8.00%)      9/66 (13.64%)    
Gastrointestinal disorders     
nausea  1  5/75 (6.67%)  5 6/66 (9.09%)  6
Nervous system disorders     
drowsiness  1  0/75 (0.00%)  0 2/66 (3.03%)  2
Skin and subcutaneous tissue disorders     
rash  1  1/75 (1.33%)  1 1/66 (1.52%)  1
Indicates events were collected by systematic assessment
1
Term from vocabulary, MedDRA (10.0)
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Prof. Herman Avner Cohen
Organization: Clalit HS
Phone: 00972 3-939-8203
Publications:
Department of child and adolescent health. Cough and cold remedies for the treatment of acute respiratory infections in young children. Geneva, Switzerland: World Health Organization: 2001.
Kraft K. Efficacy of fluid in Plantago lanceolata extract (PLFE) in acute respiratory disease. Phytomedicine, Supplement 1, 1996
Responsible Party: Avner Herman Cohen, Clalit Health Services
ClinicalTrials.gov Identifier: NCT01968434     History of Changes
Other Study ID Numbers: COM-13-00
First Submitted: October 17, 2013
First Posted: October 24, 2013
Results First Submitted: May 14, 2015
Results First Posted: November 2, 2015
Last Update Posted: February 23, 2018