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

Tracking Information

• First Submitted Date: October 17, 2013
• First Posted Date: October 24, 2013
• Results First Submitted Date: May 14, 2015
• Results First Posted Date: November 1, 2015
• Last Update Posted Date: February 23, 2018
• Study Start Date: December 2013
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 25, 2018)

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.

Original Primary Outcome Measures (submitted: October 19, 2013)

reduction in night cough severity [ Time Frame: 8 months ]

Night cough severity is most bothersome to the child and family. The questionnaire rating night cough is filled in each morning relating to the passed night for four nights. The basal night score is the score of the night before enrollment.

Current Secondary Outcome Measures (submitted: October 5, 2015)

• 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.
• 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.

Original Secondary Outcome Measures (submitted: October 19, 2013)

reduction in day cough severity [ Time Frame: 8 months ]

The questionnaire rating day cough is filled in each evening relating to the passed day for three days. The basal day score is the score of the day before enrollment.

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Comparison of Efficacy and Tolerability of Two Cough Syrups in Cough Due to Cold in Children.
• 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
• 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).

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 Type: Interventional
• Study Phase: Phase 4
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Single (Outcomes Assessor); Primary Purpose: Treatment

Condition

• Cough
• Upper Respiratory Tract Infection

Intervention

• 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
• Drug: carbocisteine cough syrup
  Mucolytic
  Other Names:

  • Mucolit
  • Lisomucil

Study Arms

• 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)

  Intervention: Device: protective cough syrup
• Active Comparator: carbocisteine cough syrup
  Dosage 20-25 mg/kg/day three times a day (3 days/4 nights)
  Intervention: Drug: carbocisteine cough syrup

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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: October 19, 2013): 150
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 2014
• Actual Primary Completion Date: March 2014 (Final data collection date for primary outcome measure)

Eligibility 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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 2 Years to 5 Years (Child)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Israel

Administrative Information

• NCT Number: NCT01968434
• Other Study ID Numbers: COM-13-00
• Has Data Monitoring Committee: No
• U.S. FDA-regulated Product: Not Provided

IPD Sharing Statement

• Plan to Share IPD: No

• Current Responsible Party: Avner Herman Cohen, Clalit Health Services
• Original Responsible Party: Same as current
• Current Study Sponsor: Clalit Health Services
• Original Study Sponsor: Same as current
• Collaborators: Aboca Spa Societa' Agricola

Investigators

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

• PRS Account: Clalit Health Services
• Verification Date: January 2018