Rice K, Rubins J, Lebahn F, et al. Withdrawal of chronic systemic corticosteroids in patients with COPD – A randomized trial. American Journal of Respiratory and Critical Care Medicine 2000;162:174-78
PubMed link: https://www.ncbi.nlm.nih.gov/pubmed/10903238
| Methods | Study design: Randomized double-blind placebo-controlled study with a parallel-design
Number of groups: Two groups |
| Participants | Number of participants: 38 randomized, 38 completed
· Active deprescribing group: 20 randomized, 20 completed · Control group: 18 randomized, 18 completed Age: 72 ± 6 years Sex: 0 female, 38 male Participants with dementia: No Inclusion criteria · Received both inhaled beta-agonists and daily oral prednisone at a dose of at least 5 mg/day for the preceding 6 months · No reduction in their maintenance dose in the past month · COPD by American Thoracic Society criteria · Age > 50 year · Cigarette-smoking history of at least 20 pack-years Exclusion criteria: · Clinical diagnosis of asthma o Including patients with normal or highly (50%) variable spirometric data within the previous 5 year o History of eosinophilia o High IgE titer o Strong family history of atopy · Concomitant major illness that would probably preclude travel to monthly appointments · Predicted survival less than 6 months Country: United States of America Setting: Community |
| Interventions | Medicine: Oral prednisolone
Withdrawal schedule: Daily maintenance prednisone dose was reduced by 5 mg/week. Note: Both groups had access to as required oral prednisolone (40mg per day) to be taken for 10 days during acute exacerbations. Comparator: Placebo compared to continued therapy |
| Outcomes | Average number of COPD exacerbations
Average daily systemic corticosteroid dose Dyspnea index Health-related quality of life Spirometric results Changes in body weight Adverse drug withdrawal effects – symptoms of steroid withdrawal |
| Dates | Dates: Not described
Duration: Six months |
| Funding sources | Not described |
| Notes |
Risk of bias table
| Bias | Authors’ judgment | Support for judgment |
| Random sequence generation (selection bias) | Unclear risk | Randomization method not clear, but probably done:
“subjects were randomly assigned to receive identically packaged dose packs that contained either their usual maintenance dose of prednisone or capsules in which the daily maintenance prednisone dose was reduced by 5 mg/week. In order to avoid an unplanned imbalance in baseline prednisone dose as a covariate that could be an indicator of the degree of steroid-dependency or severity of illness, patients were stratified according to whether their maintenance prednisone dose was: 5 to 10 mg/d or more than 10 mg/d. Patients were then randomly assigned to treatment so that pre-determined, approximately equal proportions of patients from each stratum received each treatment.” |
| Allocation concealment (selection bias) | Unclear risk | Not described |
| Blinding of participants and personnel (performance bias) | Low risk | Study claims placebo-controlled and double-blind. Placebo not adequately described but probably done.
“receive identically packaged dose packs that contained either their usual maintenance dose of prednisone or capsules in which the daily maintenance prednisone dose was reduced by 5 mg/week.” “By the end of the study 38% (95% CI: 19 to 63%) of patients in the continuous group and 57% (95% CI: 30 to 78%) of patients in the demand group correctly guessed their treatment assignment, neither percentage of which differed significantly from the value of 50% expected by chance” “the study coordinator (F.L.) correctly guessed the treatment assignment of 76% (95% CI: 51 to 91%) of the patients in the continuous group and of 85% (95% CI: 59 to 96%) of the patients in the demand group, both of which percentages are significantly better than would be expected by chance. Her judgment was based on subtle improvements in patients’ appearance and affect in the demand group.” |
| Blinding of outcome assessment (detection bias) | Unclear risk | As above |
| Incomplete outcome data (attrition bias) | Low risk | Differences in withdrawal rates and other proportions were analyzed with chi-square tests, and time to exacerbation and time on study drug were evaluated through Kaplan–Meier survival analysis. Differences in spirometric data, dyspnea, and quality of life indices were analyzed with unpaired t-tests. Treatment outcomes relating to COPD exacerbations and systemic corticosteroid exposure were determined with an intention-to-treat analysis. |
| Selective reporting (reporting bias) | Low risk | The described outcomes are all reported. |
| Other bias | Low risk | No report of funding or conflicts |
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