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

• ClinicalTrials.gov Identifier: NCT01968434
• Recruitment Status: Completed
• First Posted: October 24, 2013
• Results First Posted: November 1, 2015
• Last Update Posted: February 23, 2018
• Sponsor: Clalit Health Services
• Collaborator: Aboca Spa Societa' Agricola
• Information provided by (Responsible Party): Avner Herman Cohen, Clalit Health Services

Study Description

Brief Summary:

The purpose of this study is to determine if there is comparable efficacy between carbocisteine and a protective cough syrup from natural ingredients in children's cough due to upper respiratory tract infections (URTI) such as the common cold. The hypothesis is that protecting the throat is very useful in decreasing cough severity, both day and night, without needing to subdue such an important reflex as cough, and without only acting on mucous fluidification, especially in children where sedation and excessive fluidification is dangerous. The research hypothesis is that the protective (Grintuss) Syrup relieves cough (frequency, intensity, degree of disturbance due to nocturnal cough, and improves the quality of sleep of the child) as much as or more than the carbocysteine syrup usually used to treat children (Syr Mucolit).

Condition or disease	Intervention/treatment	Phase
Cough; Upper Respiratory Tract Infection	Device: protective cough syrup; Drug: carbocisteine cough syrup	Phase 4

Detailed Description:

Cough is a life saving reflex, therefore it is important, especially in pediatrics, to calm cough spells without sedating the reflex. Mucolytic agents have been shown to be helpful but side effects have been reported and use has been prohibited under 2 years of age. Therefore, a completely safe and effective cough remedy has not been officially reported yet in a randomised trial. Looking into other mechanisms for cough management such as protection of irritated pharynx mucosa from post nasal drip or other irritating substances is theoretically sound and shows practical interesting results.

A parallel comparison of efficacy and tolerability between such protective mechanism (acting through a barrier and radical scavenging action) due to natural substances (honey, plantago lanceolata, grindelia robusta and helichrysum italicum) and a mucolytic substance has not been done so far, in young children, especially in a time frame of 4 days. The intent of this study is to use the protective syrup versus carbocysteine in children with moderate to severe night and daily cough, measured with a validated parent questionnaire. The invasiveness of cough is followed immediately after one night administration of the study products and daily for four days.

A similar effectiveness of the protective cough syrup as compared to carbocisteine is considered very interesting due to the mechanism of the remedy.

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 150 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Randomized, Single Blind, Multicenter Study to Evaluate the Efficacy and Tolerability of Syr. Grintuss Pediatric and Syr. Mucolit in Cough Due to Upper Respiratory Tract Infection in Children
• Study Start Date: December 2013
• Actual Primary Completion Date: March 2014
• Actual Study Completion Date: April 2014

Arms and Interventions

Arm	Intervention/treatment
Experimental: protective cough syrup; 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)	Device: 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.; Other Name: Grintuss
Active Comparator: carbocisteine cough syrup; Dosage 20-25 mg/kg/day three times a day (3 days/4 nights)	Drug: carbocisteine cough syrup; Mucolytic; Other Names: Mucolit; Lisomucil

Outcome Measures

Primary Outcome Measures :

1. Change in Night Cough Score on First Night of Treatment (From N0 to N1) [ Time Frame: 1 night from before enrollment (N0) to first night after treatment (N1) ]
   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.

Secondary Outcome Measures :

1. Change in Night Cough Score at End of Study (From N0 to N4) [ Time Frame: 4 nights (onset of trial Night 1 to Night 4) and 3 days ]
   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.
2. Change in Day Cough Score at End of Study (From D0 to D4) [ Time Frame: 4 nights (onset of trial Night 1 to Night 4) and 3 days ]
   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.

Eligibility Criteria

• Ages Eligible for Study: 2 Years to 5 Years (Child)
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria:

• cough attributed to URTI such as the common cold
• 2-5 years of age
• moderate to severe day cough according to questionnaire (score at least 3 on all 3 questions relating to day cough) considering the day prior to enrollment.
• moderate to severe night cough score according to questionnaire (score at least 3 of 2 of the three questions relating to the evaluation of nocturnal cough (frequency of nocturnal cough, impact of the sleep of the child and impact on the sleep of the parent)
• signature of informed consent

Exclusion Criteria:

• Children with the diagnosis of diseases of the lower respiratory tract: inflammation of the larynx, trachea, bronchi, pneumonia, asthma, sinusitis, allergic rhinitis, as well as heart disease.
• Children who received cough medicines or drugs containing antihistamines the day prior to study entry.
• Known hypersensitivity to honey or any other component of the experimental product such as Grindelia, Helichrysum, essential oils natural flavourings of Lemon, Sweet Orange, Myrtle; Lemon natural flavouring
• Children who received any steroid preparation (spray nozzle , or syrup , or other similar the day before study entry )
• Known sensitivity to carbocysteine specifically to the comparator Mucolit
• gastric ulcer

Contacts and Locations

Locations

Israel

Pediatric Ambulatory Clinic Bat-Yam

Bat Yam, Israel

Pediatric Ambulatory Clinic Kfar-Saba

Kfar Saba, Israel

Pediatric Community Ambulatory Clinic - Petach-Tikva

Petaẖ Tiqwa, Israel

Pediatric Ambulatory Clinic Ramat Aviv Gimel

Tel Aviv, Israel

Sponsors and Collaborators

Clalit Health Services

Aboca Spa Societa' Agricola

Investigators

• Principal Investigator: Herman Avner Cohen, Professor; Clalit Health Services

More Information

Publications:

Middleton KR, Hing E. National Hospital Ambulatory Medical Care Survey: 2004 outpatient department summary. Adv Data. 2006 Jun 23;(373):1-27.

Paul IM, Yoder KE, Crowell KR, Shaffer ML, McMillan HS, Carlson LC, Dilworth DA, Berlin CM Jr. Effect of dextromethorphan, diphenhydramine, and placebo on nocturnal cough and sleep quality for coughing children and their parents. Pediatrics. 2004 Jul;114(1):e85-90. doi: 10.1542/peds.114.1.e85.

Paul IM, Beiler J, McMonagle A, Shaffer ML, Duda L, Berlin CM Jr. Effect of honey, dextromethorphan, and no treatment on nocturnal cough and sleep quality for coughing children and their parents. Arch Pediatr Adolesc Med. 2007 Dec;161(12):1140-6. doi: 10.1001/archpedi.161.12.1140.

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.

Allen KL, Molan PC, Reid GM. A survey of the antibacterial activity of some New Zealand honeys. J Pharm Pharmacol. 1991 Dec;43(12):817-22. doi: 10.1111/j.2042-7158.1991.tb03186.x.

Schramm DD, Karim M, Schrader HR, Holt RR, Cardetti M, Keen CL. Honey with high levels of antioxidants can provide protection to healthy human subjects. J Agric Food Chem. 2003 Mar 12;51(6):1732-5. doi: 10.1021/jf025928k.

Cohen HA, Rozen J, Kristal H, Laks Y, Berkovitch M, Uziel Y, Kozer E, Pomeranz A, Efrat H. Effect of honey on nocturnal cough and sleep quality: a double-blind, randomized, placebo-controlled study. Pediatrics. 2012 Sep;130(3):465-71. doi: 10.1542/peds.2011-3075. Epub 2012 Aug 6.

Bogdanov S, Jurendic T, Sieber R, Gallmann P. Honey for nutrition and health: a review. J Am Coll Nutr. 2008 Dec;27(6):677-89. doi: 10.1080/07315724.2008.10719745.

Rimsza ME, Newberry S. Unexpected infant deaths associated with use of cough and cold medications. Pediatrics. 2008 Aug;122(2):e318-22. doi: 10.1542/peds.2007-3813.

Kraft K. Efficacy of fluid in Plantago lanceolata extract (PLFE) in acute respiratory disease. Phytomedicine, Supplement 1, 1996

Wegener T, Kraft K. [Plantain (Plantago lanceolata L.): anti-inflammatory action in upper respiratory tract infections]. Wien Med Wochenschr. 1999;149(8-10):211-6. German.

• Responsible Party: Avner Herman Cohen, MD. Head Dep. Pediatric Ambulatory Clinic -Petah-Tikva, Israel, Clalit Health Services
• ClinicalTrials.gov Identifier: NCT01968434
• Other Study ID Numbers: COM-13-00
• First Posted: October 24, 2013
• Results First Posted: November 1, 2015
• Last Update Posted: February 23, 2018
• Last Verified: January 2018

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: No

Keywords provided by Avner Herman Cohen, Clalit Health Services:

cough; common cold; antitussive agents; mucosal protection; medical device

Additional relevant MeSH terms:

Infections; Respiratory Tract Infections; Cough; Respiration Disorders; Respiratory Tract Diseases; Signs and Symptoms, Respiratory; Carbocysteine; Anti-Infective Agents, Local; Anti-Infective Agents; Expectorants; Respiratory System Agents