Summary of findings for the main comparison. Macrolide+tetracycline versus macrolide.
| Macrolide+tetracycline compared to macrolide for chronic obstructive pulmonary disease | ||||||
| Patient or population: chronic obstructive pulmonary disease Setting: 16 centres across Australia and New Zealand Intervention: roxithromycin (continuous; 300 mg daily) + doxycycline (continuous; 100 mg daily) Comparison: roxithromycin (continuous; 300 mg daily) | ||||||
| Outcomes | Anticipated absolute effects* (95% CI) | Relative effect (95% CI) | № of participants (studies) | Certainty of the evidence (GRADE) | Comments | |
| Risk with macrolide | Risk with Macrolide+tetracycline | |||||
|
Quality of life, measured by CRQ (dyspnoea, fatigue, emotional function, and mastery subscales) Follow‐up 12 weeks (end of treatment) Scale from 0 to 10. Higher scores on the scale indicates better quality of life |
The mean change in CRQ HRQoL (dyspnoea) was 2.21 |
MD 0.58 higher (0.84 lower to 2.00 higher) | ‐ | 187 (1 RCT) | ⊕⊝⊝⊝ Very lowa,b,d | An increase of three points in this domain refers to a clinically significant reduction in dyspnoea (Jaeschke 1989; Jones 2002) |
| The mean change in CRQ HRQoL (fatigue) was 0.68 |
MD 0.02 higher (1.08 lower to 1.12 higher) | ‐ | 187 (1 RCT) | ⊕⊝⊝⊝ Very lowa,b,d,e | An increase of four points in this domain refers to a clinically significant reduction in fatigue (Jaeschke 1989; Jones 2002) | |
| The mean change in CRQ HRQoL (emotional function) was 0.45 |
MD 0.37 lower (1.74 lower to 1.00 higher) | ‐ | 187 (1 RCT) | ⊕⊝⊝⊝ Very lowa,b,d,f | An increase of two points in this domain refers to a clinically significant improvement in emotional function (Jaeschke 1989; Jones 2002) | |
| The mean change in CRQ HRQoL (mastery) was 0.53 |
MD 0.79 lower (1.86 lower to 0.28 higher) | ‐ | 187 (1 RCT) | ⊕⊝⊝⊝ Very lowa,b,d,f | No reported minimally important difference (MID) | |
|
All‐cause serious adverse events 60 weeks (end of study) |
237 per 1000 | 237 per 1000 (139 to 375) | OR 1.00 (0.52 to 1.93) | 198 (1 RCT) | ⊕⊝⊝⊝ Very lowa,d,e,g | |
|
Lung function (trough FEV1) Change from baseline to 12 weeks (end of active treatment) |
The mean change in trough FEV1 was 0.047 L | MD 0.01 L lower (0.09 lower to 0.07 higher) | 182 (1 RCT) | ⊕⊝⊝⊝ Very lowa,b,d,f | An improvement of 100 mL (0.1 L) for FEV1 trough is considered clinically significant (Donohue 2005) | |
|
All‐cause mortality 60 weeks (end of study) |
31 per 1000 | 49 per 1000 (12 to 183) | OR 1.63 (0.38 to 7.02) | 198 (1 RCT) | ⊕⊝⊝⊝ Very lowa,b,d | |
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Number of people experiencing one or more exacerbations, Drug resistance/microbial sensitivity (as reported by trialists), including emergence of atypical bacteria, Number of participants colonised with Pseudomonas aeruginosa |
Information for these outcomes was not presented as data for head‐to‐head comparisons were not available | |||||
| *The risk in the intervention group (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI). CI: confidence interval; CRQ: Chronic Respiratory Questionnaire; FEV1: forced expiratory volume in one second; HRQoL: health‐related quality of life; MD: mean difference; OR: odds ratio; RCT: randomised controlled trial. | ||||||
| GRADE Working Group grades of evidence High certainty: we are very confident that the true effect lies close to that of the estimate of the effect. Moderate certainty: we are moderately confident in the effect estimate; the true effect is likely to be close to the estimate of the effect, but there is a possibility that it is substantially different. Low certainty: our confidence in the effect estimate is limited; the true effect may be substantially different from the estimate of the effect. Very low certainty: we have very little confidence in the effect estimate; the true effect is likely to be substantially different from the estimate of effect. | ||||||
aThe evidence was downgraded by 1 due to attrition bias in the combined treatment arm. bThe evidence was downgraded by 2 due to indirectness of population and intervention. The aim was to assess eradication of C pneumoniae and not antibiotic prophylaxis. The comparison of interventions was not an inclusion criterion of this systematic review. cThe evidence was downgraded by 1 due to imprecision. The confidence interval crossed the line of no effect, and failed to exclude worsening of the outcome. dThe evidence was downgraded by 1 due to imprecision. The sample size was small, however, the confidence intervals fell within the minimally important difference for the outcome. eThe evidence was downgraded by 1 due to imprecision. The confidence intervals failed to exclude an important improvement or worsening of the outcome. fThe evidence was downgraded by 1 due to imprecision. The confidence interval crossed the line of no effect, and failed to exclude an important improvement of the outcome. gThe evidence was downgraded by 1 due to indirectness. The time frame when the outcome was measured (at 48 weeks follow‐up after the 12‐week active treatment period) was not included in the inclusion criteria of this review.