A Pilot Study to Determine the Feasibility and Utility of Implementing of the Full Scale TOM Trial (SAPS)

University of California San Diego

Status and phase: Completed; Phase 4

Conditions: Asthma

Treatments: Drug: ipratropium; Drug: Fluticasone 250 mg/salmeterol 50 mg; Drug: Theophylline 400 mg; Drug: Montelukast 10mg

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT01696214

ARCTC-09

IR34HL109482-01A1 (Other Grant/Funding Number)

Details and patient eligibility

About

The primary aim of the pilot (SAPS) protocol is to determine the feasibility and utility of implementing the provisional design of the full scale TOM trial (e.g., the six month treatment period, the impact of the smoking cessation intervention).

There is no active hypothesis for the Vanguard Protocol.

Full description

The protocol is a small scale pilot of the full-scale TOM trial, and it will utilize a placebo design and incorporates 4 treatment arms. In the Vanguard Protocol all participants are to complete a 4 week run-in with Advair 100/50, followed by randomization to 1 of 4 arms of study treatment. The 4 drug treatment combinations are (2 inhalers, 2 pills):

• Advair 250/50, Placebo, Placebo, Placebo
• Advair 100/50 and montelukast, Placebo, Placebo
• Advair 100/50 and theophylline, Placebo, Placebo
• Advair 100/50 and ipratropium, Placebo, Placebo The 24 week treatment phase will be followed by a 4 week washout period on Advair 100/50. There is no crossover.

Enrollment: 20 patients

Sex: All

Ages: 18 to 50 years old

Volunteers: No Healthy Volunteers

Inclusion criteria

• Gender and Age:
• Males and females, ages 18- 50

Current Smoker:

• Smoke at least 5 cigarettes per day for at least 5 years
• Positive urine cotinine test

Asthma:

• Physician diagnosed asthma

• Symptomatic, as evidenced by

  • Use of SABA two or more times per week for relief of asthma symptoms, or
  • One or more nocturnal awakenings per week for asthma symptoms ACRC - SC MEETING - 19 MAY 2012 SAPS │ 25 Confidential, not for attribution or citation.

• Pre-BD FEV1 greater than or equal to 40% predicted

• Asthma diagnosis confirmed by either

  • albuterol reversibility of FEV1 by 12% or more, or
  • 20% fall in FEV1 at 8mg or less of methacholine

• If over age 45, a DLco greater than 80% predicted

• Females of childbearing potential: not pregnant, not lactating and agree to practice an adequate birth control method (abstinence, combination barrier and spermicide, or hormonal) for the duration of the study.

Exclusion criteria

• Diagnosis of COPD or emphysema

• Other major chronic illnesses in the opinion of the investigator that might interfere with the study:

  • e.g. including but not limited to uncontrolled diabetes, uncontrolled HIV infection or other immune system disorder, hyperthyroidism, seizure disorders, renal failure, liver disease, non-skin cancer, unstable psychiatric illness.

• Recent active substance abuse (in past 6 months)

• Lung disease other than asthma including COPD, bronchiectasis, sarcoidosis, or other significant lung disease

• Unstable cardiac disease (decompensated CHF, unstable angina, recent MI, atrial fibrillation, supraventricular or ventricular tachycardia, congenital heart disease, or severe uncontrolled hypertension).

• High risk of near fatal or fatal asthma as defined by the following 1-3

  • ICU admission of asthma in the past year
  • more than 2 hospitalizations for asthma in the previous year
  • more than 3 ED visits for asthma in the previous year
  • intubation or ICU admission for asthma in the past 2 years
  • use of more than 2 canisters of inhaled short-acting beta2-agonist in past month

• Acute asthma exacerbation in the past 4 weeks (treatment with systemic corticosteroids)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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20 participants in 4 patient groups, including a placebo group

Ipratropium

Placebo Comparator group

Description:

Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and be assigned to a 24 week treatment of ipratropium 2.5 mL, 0.02% 3 times daily via mini nebulizer with placebo theophylline and placebo montelukast.

Treatment:

Drug: ipratropium

Theophylline

Placebo Comparator group

Description:

Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to theophylline 400 mg once a day for 24 weeks with placebo ipratropium and placebo montelukast.

Treatment:

Drug: Theophylline 400 mg

Montelukast

Placebo Comparator group

Description:

Participants will continue fluticasone 100 mg/salmeterol 50 mg once a day and will be assigned to montelukast 10 mg once a day for 24 weeks with placebo theophylline and placebo ipratropium.

Treatment:

Drug: Montelukast 10mg

fluticasone 250 mg/salmeterol 50mg

Placebo Comparator group

Description:

Participants will be assigned to inhaled fluticasone 250/salmeterol 50 twice a day for 24 weeks with placebo theophylline, placebo ipratropium, and placebo montelukast.

Treatment:

Drug: Fluticasone 250 mg/salmeterol 50 mg