A double blind randomised placebo controlled pilot study of oral co-trimoxazole in advanced fibrotic lung disease

Abstract

Background: In 1996, clinical improvement with oral co-trimoxazole was noted in a patient with biopsy proven advanced fibrotic lung disease who was awaiting a lung transplant. Subsequently, 14 patients with end stage fibrotic lung disease also responded to oral co-trimoxazole. This prompted a double blind randomised placebo controlled pilot study in patients with advanced stages of idiopathic interstitial pneumonias (IIP) to objectively measure benefit. Patients: Twenty patients (aged 49–84 years; 11 males) with progressive fibrotic lung disease who had differing subtype diagnosis from CT scans of progressive fibrotic IIP, and showed oxygen desaturation on exertion were selected. Method: A detailed assessment of arterial gases, lung function, and progressive shuttle-walking tests combined with oxygen saturation monitoring. Quality of life data was recorded. Randomisation was to co-trimoxazole or identical placebo for 3 months followed by 6 weeks of pulmonary rehabilitation before decoding. Placebo patients received active treatment upon decoding with continued follow up of all patients. Main outcome measures: Primary 1. Shuttle walking test. Secondary 2. FVC and quality of life. Results: Active treatment showed a significant improvement in shuttle walking test from 255 to 355 m ( p = 0.002 ) (95% CI 200–450) with reduced oxygen desaturations during exercise ( p = 0.003 ). FVC improved on treatment (+21%) from median 1.9 to 2.3 L ( p = 0.05 ) (95% CI 1.3–3.0) but TLC and DLCO were not significantly changed although stable at 12 months. The MRC 5 Point Dyspnoea Score showed improvement ( p = 0.05 ) at 3 months for the active group which was maintained at 12 months. The SGHRQ showed a significant reduction in symptom scores at 12 months ( p = 0.05 ). The placebo group showed no significant change in any parameters, but demonstrated identical improvement following oral co-trimoxazole. Serum vascular endothelial growth factor (VEGF) was reduced 50% in the active group at 3 months, but just failed to reach statistical significance. ‘Out of study’ HRCT scans in 12 patients showed significant reduction in ground glass changes ( p = 0.05 ) after 12 months of continuous co-trimoxazole treatment. Conclusion: The findings of the pilot study show significant improvements in objective and subjective parameters which fulfil the ATS/ERS (2000) criteria of ‘a favourable response to treatment’.