Thomas 1992.
| Methods | 1) Randomisation: not described. 2) Allocation concealment: not described. 2) Masking: Double blind. Placebo was indistinguishable from the active medication. 3) Withdraw/Drop‐out: Two drop‐out (one during the theophylline titration period for reasons unrelated to the study and the other during the second treatment phase due to severe dyspnoea ‐ at which time he was receiving theophylline. 4) Duration of intervention: 2 weeks x 4. Four arms in study but we need only use 2 (3 versus 4). 6) Design: Crossover groups 7) Jadad quality score: 4 8) Location: Toronto, Canada | |
| Participants | 1) Inclusion criteria: Stable COPD, outpatients. 2) Definition of COPD: FEV1 less than 60 % of predicted normal and FEV1/FVC ratio less than 0.7. 3) Definition of stable COPD: not requiring additional therapeutic intervention. 5) Age: Mean= 63.1 years ( SD 4.6 years). 6) FEV1: Mean= 1.09 L (SD 0.35 and range 0.6 to 1.6 L) 7) Number of patients: 12 (6 men and 6 women). Withdraw: 2 .Initial number of patients: 14 patients. 8) Baseline therapy: No bronchodilators, other than the test medications or steroids were allowed during the trial. Medications patients were taking at time of study entry were continued at stable dosages throughout the trial. 9) Exclusion criteria: FEV1 or FVC values differed by more than 20 % in any spirometric tests performed during the preceding two years. Evidence of severe cardiac, hepatic, or renal disease; and if taking allopurinol, beta‐blockers, oral corticosteroids, phenytoin, or cimetidine. | |
| Interventions | THEOPHYLLINE GROUP (n = 12, completed the study)
1) Drug: Phyllocontin, Purdue Frederick.
2) Short or long action: Long‐action theophylline.
3) Dose: twice daily, at a previously determined dosage.
4) Washout: not reported.
5) Theophylline blood level: measured on the open‐label theophylline dose‐titration period during which their dosage of oral was adjusted to produce serum theophylline concentration of at least 10 mg/L, and as close as possible to 16.5 mg/L ‐ between 4 and 6 h after dose. PLACEBO GROUP (n=12) |
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| Outcomes | 1) Pulmonary function tests: FVC (L), FEV1 (L), FVC, IC, FRC, Raw, TLC, RV. 2) Patient diary data. 3) Dyspnoea, cough, wheezing and sputum production: using a five‐point simple scale 0 = none; 1 = mild; 2 = moderate; 3 = severe; 4 = intolerable. 4) Side effects: using a simple five‐point scale 0 = none; 1= mild; 2 = moderate; 3 = severe; 4 = intolerable. | |
| Notes | 1) Intention‐to‐treat analyses: No. 2) Sample size and statistical power: not reported. 3) Representativity: not described. | |
| Risk of bias | ||
| Bias | Authors' judgement | Support for judgement |
| Allocation concealment (selection bias) | Unclear risk | B ‐ Unclear |
6MW: Six minute walk distance AT: Anaerobic threshold (mlVO2/min) DLCO: Diffusing capacity of the lung for carbon monoxide (ml/min/mmHg) FEV1: Forced expiratory volume in one second (L) FVC: Forced Vital Capacity (L) FRC: Functional Residual Capacity (L) HR: Heart Rate MMFER: Maximal mid flow expiratory rate MVV: Maximum Voluntary Ventilation (L) PaCO2: Arterial carbon dioxide tension (mmHg or KPa) PaO2: Arterial oxygen tension (mmHg or KPa) PC20: concentration of inhalent necessary to produce a 20% fall in FEV1 PEFR: Peak expiratory flow rate RV: Residual volume (L) SVC: Slow vital capacity (L) TGV: Trapped gas volume (L) TLC: Total Lung Capacity (L) VEmax/MVV: dyspnoea index VE/VO2slope: anaerobic threshold VO2max/HR : maximum oxygen pulse VO2 max: Maximum oxygen consumption WR: Work Rate