Lung Health Study II (LHSII)

University of Minnesota (UMN)

Status and phase: Completed; Phase 3

Conditions: Lung Diseases, Obstructive; Lung Diseases; Chronic Obstructive Pulmonary Disease

Treatments: Other: Placebo; Drug: triamcinolone

Study type: Interventional

Funder types: Other; NIH

Identifiers

NCT00000569

9109M04382

5U01HL050267-03 (U.S. NIH Grant/Contract)

Details and patient eligibility

About

To determine if participants with chronic obstructive pulmonary disease, who were assigned to inhaled corticosteroids had a lower rate of decline in lung function and lower incidence of respiratory morbidity compared to participants assigned to placebo.

Full description

BACKGROUND:

Chronic obstructive pulmonary disease (COPD), the fourth leading cause of death in the United States and a major cause of morbidity, is a spectrum of chronic lung diseases including clinical diagnoses of chronic bronchitis, emphysema, and combinations of both. Varying degrees of bronchoreactivity occur over the entire spectrum. Asthma and COPD have many features in common. Distinction is usually dependent on clinical features and clinical course. The diagnosis of asthma will not exclude a patient from the designation of COPD for this study, although criteria for exclusion include recent (within six months) use of inhaled or oral steroid with the intent of excluding most of those who are clearly predominantly bronchospastic. The morbid anatomy of COPD is well described and includes many features of acute and chronic inflammation. There is well supported evidence in the literature that this inflammatory process may be an important pathogenetic mechanism in the development of emphysema. On this basis, the rationale for the use of corticosteroids is well justified. There are various published studies suggesting that inhaled steroids reduce bronchial lavage markers of inflammation, variously influence short-term bronchial hyperreactivity, improve lung function acutely or short-term, and slow rate of decline in lung function. Most studies have asked for improvement rather than stability. However, despite the studies which do not support these contentions and the lack of long-term information, inhaled steroids in COPD are becoming widely used in clinical practice. It was the intent of this clinical trial to assess the long-term efficacy of this treatment before such therapy became an accepted community practice, making it impractical or impossible to conduct a clinical trial.

DESIGN NARRATIVE:

Subjects were recruited from the Lung Health Study I and randomized to 1200 micrograms of triamcinolone in daily divided doses or to placebo. Pulmonary function was evaluated every six months. Bronchial activity was tested at baseline, at nine months, and at three-and-a-half years using a methacholine inhalation challenge. Mean duration of follow-up was 40 months. The primary outcome measure was the rate of decline in pulmonary function as assessed by the post-bronchodilator forced expiratory volume at one second (FEV1) value. Other outcome measures included death, respiratory symptoms, quality of life, side-effects and toxicity, adherence, bronchial hyperreactivity, atopic status, and smoking status. Recruitment was initiated in November 1994 and ended November 28, 1995 to allow 3.5 to 4.5 years of follow-up through April, 1999.

The investigators initiated a dose monitor (puff counter) protocol at nine of the centers among the fair to satisfactory compliers (4 to 9 puffs versus the ideal of 12 puffs per day) to test whether a memory aid would enhance inhaler compliance. Consenting participants were randomized to Group 1 who could see the display on the puff counter for 12 months or to Group 2 who had no counter for three months, a counter that recorded but did not display for three months, and a counter with display for six months.

There were a bone densitometry and adrenal suppression ancillary studies, funded by Rhone-Poulenc-Rorer, to assess the effect of inhaled corticosteroids on bone density and adrenal function.

Enrollment: 1,116 patients

Sex: All

Ages: 40 to 69 years old

Volunteers: No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion:

1. Previously participated in or screened for the Lung Health Study I
2. Ages 40 to 69
3. Forced expiratory volume at one second (FEV1)/forced vital capacity(FVC) < 70 percent
4. Forced expiratory volume at one second (FEV1) 30 to 90 percent predicted.

Exclusions:

1. Cancer
2. Recent myocardial infarction
3. Alcoholism
4. Heart Failure
5. Insulin-dependent diabetes mellitus
6. Neuropsychiatric disorders
7. Used bronchodilators or oral or inhaled corticosteroids in previous year

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

---

1,116 participants in 2 patient groups, including a placebo group

Triamcinolone

Active Comparator group

Description:

1200 micrograms of triamcinolone in daily divided doses

Treatment:

Drug: triamcinolone

Placebo

Placebo Comparator group

Description:

Placebo

Treatment:

Other: Placebo