The Leukotriene Modifier Or Corticosteroid or Corticosteroid-Salmeterol Trial

• Sponsor: JHSPH Center for Clinical Trials (Other)
• Overall Status: Completed
• CT.gov ID: NCT00156819
• Collaborator: GlaxoSmithKline (Industry)
• Enrollment: 500
• Locations: 19
• Arms: 3
• Duration (Months): 38
• Patients Per Site: 26.3
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

This research study will compare the treatment effects of three different asthma medications in asthma subjects whose asthma is well controlled when they take fluticasone, an inhaled corticosteroid. The treatments are fluticasone, montelukast (an anti?leukotriene drug), and a combination therapy of fluticasone and salmeterol (a long-acting beta-agonist). Fluticasone, montelukast, and the combination therapy of fluticasone and salmeterol (Advair Diskus®) are all approved for the treatment of asthma. We are looking at whether the three treatments are equally effective for reducing the number and the severity of asthma attacks in subjects with mild to moderately severe asthma.

Condition or Disease	Intervention/Treatment	Phase
Asthma	Drug: fluticasone; Drug: montelukast; Drug: Fluticasone plus salmeterol	Phase 4

Detailed Description

This trial will attempt to investigate whether asthmatic patients that are well controlled with low-dose twice daily inhaled corticosteroid (ICS) therapy can safely be switched to other modes of controller therapy without loss of asthma control. Patients demonstrating good control on twice-daily low-dose ICS will be randomized to one of three treatment groups: once-daily low-dose ICS (fluticasone), leukotriene receptor antagonist (montelukast), or once-daily combination therapy (fluticasone-salmeterol).

Study Design

• Study Type: Interventional
• Actual Enrollment: 500 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: The Leukotriene Modifier Or Corticosteroid or Corticosteroid-Salmeterol Trial
• Study Start Date: Jun 1, 2003
• Actual Primary Completion Date: Aug 1, 2005
• Actual Study Completion Date: Aug 1, 2006

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Fluticasone Participants continued fluticasone (100 microgram twice daily) treatment.	Drug: fluticasone; fluticasone (100 microgram twice daily) treatment; Drug: montelukast; Montelukast (5 or 10 mg each night).; Drug: Fluticasone plus salmeterol; fluticasone (100 microgram) plus salmeterol (50 microgram) each night
Experimental: Montelukast Participants were changed to Montelukast (5 or 10 mg each night).	Drug: fluticasone; fluticasone (100 microgram twice daily) treatment; Drug: montelukast; Montelukast (5 or 10 mg each night).; Drug: Fluticasone plus salmeterol; fluticasone (100 microgram) plus salmeterol (50 microgram) each night
Experimental: Fluticasone plus salmeterol Participants were given fluticasone (100 microgram) plus salmeterol (50 microgram) each night.	Drug: fluticasone; fluticasone (100 microgram twice daily) treatment; Drug: montelukast; Montelukast (5 or 10 mg each night).; Drug: Fluticasone plus salmeterol; fluticasone (100 microgram) plus salmeterol (50 microgram) each night

Outcome Measures

Primary Outcome Measures

1. Treatment Failure [16 weeks]

   The primary outcome measure was treatment failure, defined as the occurrence of any one of the following events: hospitalization or an urgent medical visit for asthma initiated by the patient or physician; use of systemic corticosteroids for asthma or need for open-label use of inhaled corticosteroids for asthma, as determined by the study physician or an asthma care provider; a decrease in prebronchodilator forced expiratory volume in 1 second (FEV1) to more than 20% below the baseline value measured at randomization; a decrease in the morning peak expiratory flow rate to more than 35% below the baseline value (the mean over the final 2 weeks of the run-in period) on 2 consecutive days; use of 10 puffs or more per day of rescue beta-agonist for 2 consecutive days (except as medication before exercise); refusal of the patient to continue because of lack of satisfaction with treatment; or judgment by a physician that the patient should stop treatment for reasons of safety.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 6 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• physician-diagnosed asthma

• age 6 or older

• pre-bronchodilator forced expiratory volume (FEV1) of at least 60% of predicted

• beta-agonist reversibility OR airways hyperreactivity by methacholine challenge

• Juniper Asthma Control Score of 1.5 or greater if not on daily controller

• good current health

Exclusion Criteria:

• current or past smoking (greater than 20 pack-years)

• chronic or current oral steroid therapy

• pregnancy, lack of effective contraception (when appropriate), lactation

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	University of Alabama at Birmingham	Birmingham	Alabama	United States	35233
2	National Jewish Hospital	Denver	Colorado	United States	80206
3	Nemour's Childrens Center	Jacksonville	Florida	United States	32207
4	University of Miami (and University of South Florida in Tampa)	Miami	Florida	United States	33136
5	Emory University	Atlanta	Georgia	United States	30322
6	Illinois Consortium (Northwestern, Univ. of Chicago, Univ. of Illinois)	Chicago	Illinois	United States	60611
7	Indiana University	Indianapolis	Indiana	United States	46202
8	Louisiana State University	New Orleans	Louisiana	United States	70112
9	University of Minnesota	Minneapolis	Minnesota	United States	55455
10	University of Missouri at Kansas City	Kansas City	Missouri	United States	64108
11	Washington University	St. Louis	Missouri	United States	63110
12	Long Island Jewish Hospital (and North Shore Hospital)	New Hyde Park	New York	United States	11040
13	New York Consortium (New York Univ. and Columbia Univ.)	New York	New York	United States	10016
14	New York Medical College	Valhalla	New York	United States	10595
15	Duke University School of Medicine	Durham	North Carolina	United States	27710
16	Ohio State University	Columbus	Ohio	United States	43210
17	Thomas Jefferson Hospital	Philadelphia	Pennsylvania	United States	19107
18	Baylor College of Medicine	Houston	Texas	United States	77030
19	Northern New England Consortium (Univ. of Vermont and other locations)	Burlington	Vermont	United States	05405

Sponsors and Collaborators

• JHSPH Center for Clinical Trials
• GlaxoSmithKline

Investigators

• Study Chair: Nicholas Anthonisen, MD, University of Winnipeg

Study Documents (Full-Text)

None provided.

More Information

Additional Information:

• American Lung Association Asthma Clinical Research Centers

Publications

None provided.

• ClinicalTrials.gov Identifier: NCT00156819
• Other Study ID Numbers: ALAACRC-03
• First Posted: Sep 12, 2005
• Last Update Posted: Dec 9, 2015
• Last Verified: Nov 1, 2015

• Keywords provided by , ,: Asthma; Asthma Control
• Additional relevant MeSH terms: Asthma; Fluticasone; Xhance; Salmeterol Xinafoate; Montelukast

Study Results

Participant Flow

Arm/Group Title	Fluticasone	Montelukast	Fluticasone Plus Salmeterol
Arm/Group Description	Participants continued fluticasone (100 microgram twice daily) treatment. fluticasone: fluticasone (100 microgram twice daily) treatment montelukast: Montelukast (5 or 10 mg each night). Fluticasone plus salmeterol: fluticasone (100 microgram) plus salmeterol (50 microgram) each night	Participants were changed to Montelukast (5 or 10 mg each night). fluticasone: fluticasone (100 microgram twice daily) treatment montelukast: Montelukast (5 or 10 mg each night). Fluticasone plus salmeterol: fluticasone (100 microgram) plus salmeterol (50 microgram) each night	Participants were given fluticasone (100 microgram) plus salmeterol (50 microgram) each night. fluticasone: fluticasone (100 microgram twice daily) treatment montelukast: Montelukast (5 or 10 mg each night). Fluticasone plus salmeterol: fluticasone (100 microgram) plus salmeterol (50 microgram) each night
Period Title: Overall Study
STARTED	169	166	165
COMPLETED	168	165	162
NOT COMPLETED	1	1	3

Baseline Characteristics

Arm/Group Title	Fluticasone	Montelukast	Fluticasone Plus Salmeterol	Total
Arm/Group Description	Participants continued fluticasone (100 microgram twice daily) treatment. fluticasone: fluticasone (100 microgram twice daily) treatment montelukast: Montelukast (5 or 10 mg each night). Fluticasone plus salmeterol: fluticasone (100 microgram) plus salmeterol (50 microgram) each night	Participants were changed to Montelukast (5 or 10 mg each night). fluticasone: fluticasone (100 microgram twice daily) treatment montelukast: Montelukast (5 or 10 mg each night). Fluticasone plus salmeterol: fluticasone (100 microgram) plus salmeterol (50 microgram) each night	Participants were given fluticasone (100 microgram) plus salmeterol (50 microgram) each night. fluticasone: fluticasone (100 microgram twice daily) treatment montelukast: Montelukast (5 or 10 mg each night). Fluticasone plus salmeterol: fluticasone (100 microgram) plus salmeterol (50 microgram) each night	Total of all reporting groups
Overall Participants	169	166	165	500
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	29.3 (14.6)	32.4 (15.4)	30.8 (14.9)	30.8 (15.0)
Sex: Female, Male (Count of Participants)
Female	103 60.9%	95 57.2%	103 62.4%	301 60.2%
Male	66 39.1%	71 42.8%	62 37.6%	199 39.8%

Outcome Measures

1. Primary Outcome

Title	Treatment Failure
Description	The primary outcome measure was treatment failure, defined as the occurrence of any one of the following events: hospitalization or an urgent medical visit for asthma initiated by the patient or physician; use of systemic corticosteroids for asthma or need for open-label use of inhaled corticosteroids for asthma, as determined by the study physician or an asthma care provider; a decrease in prebronchodilator forced expiratory volume in 1 second (FEV1) to more than 20% below the baseline value measured at randomization; a decrease in the morning peak expiratory flow rate to more than 35% below the baseline value (the mean over the final 2 weeks of the run-in period) on 2 consecutive days; use of 10 puffs or more per day of rescue beta-agonist for 2 consecutive days (except as medication before exercise); refusal of the patient to continue because of lack of satisfaction with treatment; or judgment by a physician that the patient should stop treatment for reasons of safety.
Time Frame	16 weeks

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Fluticasone	Montelukast	Fluticasone Plus Salmeterol
Arm/Group Description	Participants continued fluticasone (100 microgram twice daily) treatment. fluticasone: fluticasone (100 microgram twice daily) treatment montelukast: Montelukast (5 or 10 mg each night). Fluticasone plus salmeterol: fluticasone (100 microgram) plus salmeterol (50 microgram) each night	Participants were changed to Montelukast (5 or 10 mg each night). fluticasone: fluticasone (100 microgram twice daily) treatment montelukast: Montelukast (5 or 10 mg each night). Fluticasone plus salmeterol: fluticasone (100 microgram) plus salmeterol (50 microgram) each night	Participants were given fluticasone (100 microgram) plus salmeterol (50 microgram) each night. fluticasone: fluticasone (100 microgram twice daily) treatment montelukast: Montelukast (5 or 10 mg each night). Fluticasone plus salmeterol: fluticasone (100 microgram) plus salmeterol (50 microgram) each night
Measure Participants	168	165	162
Number [participants]	34 20.1%	50 30.1%	33 20%

Adverse Events

Arm/Group Title	Fluticasone		Montelukast		Fluticasone Plus Salmeterol
Arm/Group Description	Participants continued fluticasone (100 microgram twice daily) treatment. fluticasone: fluticasone (100 microgram twice daily) treatment montelukast: Montelukast (5 or 10 mg each night). Fluticasone plus salmeterol: fluticasone (100 microgram) plus salmeterol (50 microgram) each night		Participants were changed to Montelukast (5 or 10 mg each night). fluticasone: fluticasone (100 microgram twice daily) treatment montelukast: Montelukast (5 or 10 mg each night). Fluticasone plus salmeterol: fluticasone (100 microgram) plus salmeterol (50 microgram) each night		Participants were given fluticasone (100 microgram) plus salmeterol (50 microgram) each night. fluticasone: fluticasone (100 microgram twice daily) treatment montelukast: Montelukast (5 or 10 mg each night). Fluticasone plus salmeterol: fluticasone (100 microgram) plus salmeterol (50 microgram) each night
All Cause Mortality
	Fluticasone		Montelukast		Fluticasone Plus Salmeterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)		/ (NaN)
Serious Adverse Events
	Fluticasone		Montelukast		Fluticasone Plus Salmeterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	6/168 (3.6%)		4/165 (2.4%)		4/162 (2.5%)
Cardiac disorders
Chest pain	1/168 (0.6%)		0/165 (0%)		0/162 (0%)
Gastrointestinal disorders
Abdominal pain	0/168 (0%)		0/165 (0%)		1/162 (0.6%)
Injury, poisoning and procedural complications
Concussion	1/168 (0.6%)		0/165 (0%)		0/162 (0%)
Anaphylactic reaction to peanuts	1/168 (0.6%)		0/165 (0%)		0/162 (0%)
Allergic reaction to Bactim	0/168 (0%)		0/165 (0%)		1/162 (0.6%)
Elbow sprain	0/168 (0%)		0/165 (0%)		1/162 (0.6%)
Abcess	0/168 (0%)		1/165 (0.6%)		0/162 (0%)
Psychiatric disorders
Depression	0/168 (0%)		0/165 (0%)		1/162 (0.6%)
Respiratory, thoracic and mediastinal disorders
Drop in peak flow	1/168 (0.6%)		1/165 (0.6%)		0/162 (0%)
Asthma exacerbation	1/168 (0.6%)		1/165 (0.6%)		0/162 (0%)
Surgical and medical procedures
Partial right knee replacement surgery	1/168 (0.6%)		0/165 (0%)		0/162 (0%)
Tonsilectomy	0/168 (0%)		1/165 (0.6%)		0/162 (0%)
Other (Not Including Serious) Adverse Events
	Fluticasone		Montelukast		Fluticasone Plus Salmeterol
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	159/168 (94.6%)		156/165 (94.5%)		157/162 (96.9%)
Gastrointestinal disorders
Nausea and vomitting	55/168 (32.7%)		35/165 (21.2%)		37/162 (22.8%)
Gastrointestinal distress	63/168 (37.5%)		57/165 (34.5%)		61/162 (37.7%)
General disorders
Hoarsness/ dysphonia	92/168 (54.8%)		78/165 (47.3%)		87/162 (53.7%)
Nasal congestion	136/168 (81%)		127/165 (77%)		129/162 (79.6%)
Headache	120/168 (71.4%)		117/165 (70.9%)		112/162 (69.1%)
Diarrhea	41/168 (24.4%)		35/165 (21.2%)		31/162 (19.1%)
Infections and infestations
Upper respiratory infection	63/168 (37.5%)		44/165 (26.7%)		62/162 (38.3%)
Pharyngitis	83/168 (49.4%)		82/165 (49.7%)		78/162 (48.1%)
Rhinitis	120/168 (71.4%)		111/165 (67.3%)		118/162 (72.8%)
Sinisitis	67/168 (39.9%)		51/165 (30.9%)		50/162 (30.9%)
Viral respiratory infection	26/168 (15.5%)		12/165 (7.3%)		22/162 (13.6%)
Influenza	15/168 (8.9%)		8/165 (4.8%)		16/162 (9.9%)
Fever	45/168 (26.8%)		25/165 (15.2%)		36/162 (22.2%)
Musculoskeletal and connective tissue disorders
Musculoskeletal pain	63/168 (37.5%)		71/165 (43%)		70/162 (43.2%)
Respiratory, thoracic and mediastinal disorders
Upper respiratory inflammation	84/168 (50%)		67/165 (40.6%)		73/162 (45.1%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.