Montelukast for Persistent Cough in Young People and Adults (MAC)

A Double Blind Randomised Placebo Controlled Trial of Montelukast in the Treatment of Acute Persistent Cough in Young People and Adults in Primary Care

Persistent cough is a common symptom, accounting for about 20% of referrals to outpatient chest clinics. Most coughs are caused by self-limiting viral infections such as the common cold. However, 1 in 4 people with a viral infection develop a persistent cough, which can go on for several weeks. Whooping cough is a common cause of persistent cough in young people and adults. Although the whooping cough vaccine gives lifelong protection against severe infection, it does not appear to give such long-term protection against milder infections, which can make someone cough for many weeks. There are currently no proven efficacious treatments for persistent cough following either a viral infection or infection with whooping cough.

Montelukast is a medication which is already licensed for the treatment of asthma. It works by blocking the action of chemicals called leukotrienes, which make the airways of people with asthma inflamed and sensitive. There is strong evidence to suggest that leukotrienes are also involved in causing persistent cough following viral or whooping cough infection. Montelukast may therefore also help settle persistent coughs in these settings.

Over 18 months, we will recruit patients aged 16-49 years with a cough lasting 2-8 weeks from general practices in England. An oral fluid sample will be taken from each participant to be tested for whooping cough. Participants will be randomly allocated to receive a 28-day course of montelukast or placebo tablets and asked to complete a daily cough diary for two weeks. They will be assessed after two weeks by their GP (face-to-face) and after four weeks by another member of practice clinical staff (telephone). Some participants will be given a 24-hour cough monitor to wear on study entry and at two-week follow-up. This study will be funded by the National Institute for Health Research's School of Primary Care.

Study Overview

• Status: Unknown
• Conditions: Whooping Cough; Persistent Cough
• Intervention / Treatment: Drug: Montelukast; Drug: Placebo

• Study Type: Interventional
• Enrollment (Actual): 276
• Phase: Phase 4

Contacts and Locations

Study Locations

• United Kingdom
  • Oxfordshire
    • Oxford, Oxfordshire, United Kingdom, OX3 7LF
      • University of Oxford

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 49 years (Child, Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Male or Female, aged 16 years to 49 years inclusive.
• Presenting with a persistent cough of 2-8 weeks' duration without an established diagnosis (e.g. asthma, gastro-oesophageal reflux).
• Able to complete cough diary and study questionnaires.

Exclusion Criteria:

• There is a contraindication to montelukast.
• Chronic severe disease which may cause persistent cough (eg cystic fibrosis, bronchiectasis, cardiac failure).
• Immunodeficiency/immunocompromised state.
• Pregnancy.
• Breastfeeding.
• Current smoker (i.e. stopped smoking less than 6 months ago).
• Regular medication associated with persistent cough (ACE inhibitors).
• The individual is in another clinical research study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Placebo Comparator: Placebo	Drug: Placebo; tablets, once per day for 28 days.
Experimental: Montelukast	Drug: Montelukast; 10mg tablets, once per day for 28 days.; Other Names: Singulair

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Change in Leicester Cough Questionnaire (LCQ) total score at 2 and 4 weeks post randomisation.	2 and 4 weeks post randomisation

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change in Leicester Cough Questionnaire (LCQ) physical, psychological and social domain scores at 2 and 4 weeks post randomisation.		2 and 4 weeks post randomisation
Overall cough severity according to cough visual analogue scale (VAS) scores over the 2-week period post randomisation (area under the curve).		2 weeks post randomisation
Paroxysmal cough severity over the 2-week period post randomisation (area under the curve).		2 weeks post randomisation
Proportions of participants reporting cessation of cough at 2 and 4 weeks post randomisation.		2 and 4 weeks post randomisation
Recruitment rate among young people and adults presenting with acute persistent cough.		End of study
Follow-up rates at 2 weeks and 4 weeks post randomisation.		2 weeks and 4 weeks post randomisation.
Medication adherence rates at 2 and 4 weeks post randomisation.		2 and 4 weeks post randomisation
Prevalence of whooping cough among participants.		End of study
Correlations between subjective cough outcome measures (diary-recorded paroxysms of cough, cough visual analogue scale score and exercise-related cough score) and objective cough frequency measured using the Leicester Cough Monitor.		2 and 4 weeks post randomisation
Proportions of participants undergoing further intervention (re-consultation, investigation, prescription of other medication).	Patient notes will be reviewed in this time frame	4 - 8 weeks
Proportions of participants with adverse events.		End of study

Collaborators and Investigators

• Sponsor: University of Oxford
• Investigators: Principal Investigator: Anthony R Harnden, University of Oxford

Publications and helpful links

General Publications

• Birring SS, Prudon B, Carr AJ, Singh SJ, Morgan MD, Pavord ID. Development of a symptom specific health status measure for patients with chronic cough: Leicester Cough Questionnaire (LCQ). Thorax. 2003 Apr;58(4):339-43. doi: 10.1136/thorax.58.4.339.
• Harnden A, Grant C, Harrison T, Perera R, Brueggemann AB, Mayon-White R, Mant D. Whooping cough in school age children with persistent cough: prospective cohort study in primary care. BMJ. 2006 Jul 22;333(7560):174-7. doi: 10.1136/bmj.38870.655405.AE. Epub 2006 Jul 7.
• Wang K, Birring SS, Taylor K, Fry NK, Hay AD, Moore M, Jin J, Perera R, Farmer A, Little P, Harrison TG, Mant D, Harnden A. Montelukast for postinfectious cough in adults: a double-blind randomised placebo-controlled trial. Lancet Respir Med. 2014 Jan;2(1):35-43. doi: 10.1016/S2213-2600(13)70245-5. Epub 2013 Dec 2.

Study record dates

Study Major Dates

• Study Start: May 1, 2011
• Primary Completion (Anticipated): October 1, 2012
• Study Completion (Anticipated): November 1, 2012

Study Registration Dates

• First Submitted: January 17, 2011
• First Submitted That Met QC Criteria: January 17, 2011
• First Posted (Estimate): January 19, 2011

Study Record Updates

• Last Update Posted (Estimate): October 10, 2012
• Last Update Submitted That Met QC Criteria: October 8, 2012
• Last Verified: October 1, 2012

More Information

Terms related to this study

• Keywords: Adults; Montelukast; Persistent cough; Double-blind randomised placebo controlled trial
• Additional Relevant MeSH Terms: Infections; Respiratory Tract Infections; Respiratory Tract Diseases; Respiration Disorders; Bordetella Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Signs and Symptoms, Respiratory; Whooping Cough; Cough; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Hormones, Hormone Substitutes, and Hormone Antagonists; Anti-Asthmatic Agents; Respiratory System Agents; Leukotriene Antagonists; Hormone Antagonists; Cytochrome P-450 CYP1A2 Inducers; Cytochrome P-450 Enzyme Inducers; Montelukast
• Other Study ID Numbers: MAC_001; 2010-019647-19 (EudraCT Number)