Wheeze and Intermittent Treatment

NCT01142505 | Completed Phase 3 DMC

• 2 other identifiers: 08/43/032009-015626-11
• Study Type: interventional
• Target: 1,358
• Locations: 1 country
• Sites: 1

Brief Summary

The clinical aim of this trial is to assess whether intermittent montelukast is an effective treatment strategy in preschool wheeze. The mechanisms aim of the trial is to determine whether there is a genetically highly-responsive subgroup of children. In designing this trial the investigators have incorporated several novel aspects. First, parents will be able to adjust the use of oral montelukast to their child's symptoms. This allows the investigators to recruit both "episodic" and "multi trigger" patterns of preschool wheeze - and control for any change in wheeze pattern during the trial. Second, before the investigators issue the trial medication, the investigators will assess children's leukotriene genes, focusing primarily on a gene called ALOX5. This ALOX5 "stratification" step will ensure that an equal number of potentially "treatment-responsive" children receive the active drug (montelukast) and the dummy medicine - and the equal numbers will help the investigators to assess the role of ALOX5. For the trial, the investigators will first recruit 1,300 children with a history of preschool wheeze, then divide them into the group with "responsive" and "less responsive" genes by their ALOX5 status. The investigators will then issue parents with the trial medication; 50% will be given montelukast and 50% will be given dummy medication. Parents will start the trial medication whenever their child develops a cold, and stop the medication when wheeze resolve. Parents will also be able to give the trial medication for wheeze between colds. Over the 12 month trial period, the investigators will assess the number of unscheduled attendances to a medical practitioner for wheeze for each child. At the end of the trial, the investigators will determine whether montelukast is effective then whether there is a difference in response to montelukast between the 2 ALOX5 gene groups. At the same time, the investigators will measure many other genes that may influence response to montelukast, as well as the amount of leukotrienes that are excreted in the urine before and during attacks. Using these results, the investigators will be able to both inform national treatment policy, and develop new concepts on the mechanism of preschool wheeze that will inform the development of new therapies. Since children will continue to receive "normal" inhaled therapy, there are no ethical issues in giving a dummy medicine to half of the 1300 children to be recruited. The study will be the largest trial in wheezy preschool children to date, and may open up genetic testing in preschool wheeze.

Conditions

Wheezing

Keywords

wheeze; preschool; leukotriene; montelukast; 5-lipoxygenase

Outcome Measures

Primary Outcomes (1)

• Need for unscheduled medical attention

  Number of times a child attends for an unscheduled medical opinion with respiratory problems over a 12 month period, as confirmed from medical records.

  12 months

Secondary Outcomes (7)

• Number of admissions to hospital

  12 months

• Duration of admissions to hospital

  12 months

• Number of unscheduled GP consultations for wheeze

  12 months

• Duration of wheezy episodes

  12 months

• Severity of episodes by diary card

  12 months

Study Arms (2)

Placebo

PLACEBO COMPARATOR

Patients in the placebo arm will be given an inactive version of the investigational medical product formed of the excipient mannitol (which is coated with the active drug montelukast in the active comparator arm)

Drug: Mannitol

Montelukast

ACTIVE COMPARATOR

Patients in the active arm will be given an active version of the investigational medical product formed of the inactive excipient mannitol with a coating of active drug montelukast.

Drug: Montelukast

Interventions

Mannitol DRUG

4mg once daily granules for 10 days, given orally alone or with cold or warm food from the onset of a cold or wheezing attack.

Also known as: Pearlitol SD 200

Placebo

Montelukast DRUG

4mg once daily granules for 10 days, given orally alone or with cold or warm food from the onset of a cold or wheezing attack

Also known as: Singulair

Montelukast

Eligibility Criteria

• Age: 10 Months - 5 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Child (0-17)

You may qualify if:

• age ≥ 10 months and ≤ 5 years old on the day of the first dose of Investigational Medicinal Product
• two or more attacks of parent-reported wheeze
• at least one attack with wheeze validated by a clinician
• the most recent attack within the last 3 months
• contactable by telephone and able to attend one face-to-face review for issue of Investigational Medicinal Product
• parent or guardian able to give written informed consent for their child to participate in the study

You may not qualify if:

• any other chronic respiratory condition diagnosed by a clinician including structural airway abnormality (e.g. floppy larynx) and cystic fibrosis
• any chronic condition that increases vulnerability to respiratory tract infection such as severe developmental delay with feeding difficulty
• history of neonatal chronic lung disease
• current continuous oral montelukast therapy
• in a trial using an Investigational Medicinal Product in the previous 3 months prior to recruitment

Sponsors & Collaborators

• Queen Mary University of London: lead
• University of Aberdeen: collaborator
• University of Leicester: collaborator

Study Sites (1)

Barts and the London NHS Trust

London, E1 1BB, United Kingdom

Location

Related Publications (2)

• Grigg J, Whitehouse A, Pandya H, Turner S, Griffiths CJ, Vulliamy T, T Walton R, Price DB, Sanak M, Holloway JW, Noimark L, Lesosky M, Brugha R, Koh L, Nwokoro C. Urinary prostanoids in preschool wheeze. Eur Respir J. 2017 Feb 2;49(2):1601390. doi: 10.1183/13993003.01390-2016. Print 2017 Feb. No abstract available.

  PMID: 28153869 DERIVED

• Nwokoro C, Pandya H, Turner S, Eldridge S, Griffiths CJ, Vulliamy T, Price D, Sanak M, Holloway JW, Brugha R, Koh L, Dickson I, Rutterford C, Grigg J. Intermittent montelukast in children aged 10 months to 5 years with wheeze (WAIT trial): a multicentre, randomised, placebo-controlled trial. Lancet Respir Med. 2014 Oct;2(10):796-803. doi: 10.1016/S2213-2600(14)70186-9. Epub 2014 Sep 8.

  PMID: 25212745 DERIVED

MeSH Terms

Conditions

Respiratory Sounds

Interventions

Mannitol; montelukast

Condition Hierarchy (Ancestors)

Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Sugar Alcohols; Alcohols; Organic Chemicals; Carbohydrates

Study Officials

• Jonathan Grigg, BSc MBBS MD

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Paediatric Respiratory Medicine

Study Record Dates

• First Submitted: June 10, 2010
• First Posted: June 11, 2010
• Study Start: November 1, 2010
• Primary Completion: February 1, 2014
• Study Completion: February 1, 2014
• Last Updated: April 29, 2014

Record last verified: 2014-04

Locations

GB (1)