Wheeze and Intermittent Treatment (WAIT)
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|ClinicalTrials.gov Identifier: NCT01142505|
Recruitment Status : Completed
First Posted : June 11, 2010
Last Update Posted : April 29, 2014
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.
|Condition or disease||Intervention/treatment||Phase|
|Wheezing||Drug: Mannitol Drug: Montelukast||Phase 3|
|Study Type :||Interventional (Clinical Trial)|
|Actual Enrollment :||1358 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)|
|Official Title:||Parent-determined Oral Montelukast Therapy for Preschool Wheeze With Stratification for Arachidonate-5-Lipoxygenase (ALOX5) Promoter Genotype|
|Study Start Date :||November 2010|
|Actual Primary Completion Date :||February 2014|
|Actual Study Completion Date :||February 2014|
Placebo Comparator: Placebo
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)
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.
Other Name: Pearlitol SD 200
Active Comparator: Montelukast
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.
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
Other Name: Singulair
- Need for unscheduled medical attention [ Time Frame: 12 months ]Number of times a child attends for an unscheduled medical opinion with respiratory problems over a 12 month period, as confirmed from medical records.
- Number of admissions to hospital [ Time Frame: 12 months ]
- Duration of admissions to hospital [ Time Frame: 12 months ]
- Number of unscheduled GP consultations for wheeze [ Time Frame: 12 months ]The number of times a child is brought to his primary care/family doctor with wheeze
- Duration of wheezy episodes [ Time Frame: 12 months ]The duration of wheezy episodes as recorded by parents on their diary cards.
- Severity of episodes by diary card [ Time Frame: 12 months ]The severity of wheeze episodes as recorded in parent diary cards
- Parent's overall impression of efficacy of Investigational Medicinal Product [ Time Frame: 12 months ]Parent's overall impression of efficacy of Investigational Medicinal Product as recorded in diary cards.
- Time to first attack of wheeze [ Time Frame: 12 months ]Time to first attack of wheeze as recorded in parent diary card and researcher phonecalls.
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01142505
|Barts and the London NHS Trust|
|London, United Kingdom, E1 1BB|
|Principal Investigator:||Jonathan Grigg, BSc MBBS MD||Queen Mary University of London|