RATIONALE: The role of antibiotics in acute exacerbations is controversial and their efficacy when added to systemic corticosteroids is unknown. OBJECTIVES: We conducted a randomized, placebo-controlled trial to determine the effects of doxycycline in addition to corticosteroids on clinical outcome, microbiological outcome, lung function, and systemic inflammation in patients hospitalized with an acute exacerbation of chronic obstructive pulmonary disease. METHODS: Of 223 patients, we enrolled 265 exacerbations defined on the basis of increased dyspnea and increased sputum volume with or without increased sputum purulence. Patients received 200 mg of oral doxycycline or matching placebo for 7 days in addition to systemic corticosteroids. Clinical and microbiological response, time to treatment failure, lung function, symptom scores, and serum C-reactive protein were assessed. MEASUREMENTS AND MAIN RESULTS: On Day 30, clinical success was similar in intention-to-treat patients (odds ratio, 1.3; 95% confidence interval, 0.8 to 2.0) and per-protocol patients. Doxycycline showed superiority over placebo in terms of clinical success on Day 10 in intention-to-treat patients (odds ratio, 1.9; 95% confidence interval, 1.1 to 3.2), but not in per-protocol patients. Doxycycline was also superior in terms of clinical cure on Day 10, microbiological outcome, use of open label antibiotics, and symptoms. There was no interaction between the treatment effect and any of the subgroup variables (lung function, type of exacerbation, serum C-reactive protein, and bacterial presence). CONCLUSIONS: Although equivalent to placebo in terms of clinical success on Day 30, doxycycline showed superiority in terms of clinical success and clinical cure on Day 10, microbiological success, the use of open label antibiotics, and symptoms. Clinical trial registered with www.clinicaltrials.gov (NCT00170222).
RCT Entities:
RATIONALE: The role of antibiotics in acute exacerbations is controversial and their efficacy when added to systemic corticosteroids is unknown. OBJECTIVES: We conducted a randomized, placebo-controlled trial to determine the effects of doxycycline in addition to corticosteroids on clinical outcome, microbiological outcome, lung function, and systemic inflammation in patients hospitalized with an acute exacerbation of chronic obstructive pulmonary disease. METHODS: Of 223 patients, we enrolled 265 exacerbations defined on the basis of increased dyspnea and increased sputum volume with or without increased sputum purulence. Patients received 200 mg of oral doxycycline or matching placebo for 7 days in addition to systemic corticosteroids. Clinical and microbiological response, time to treatment failure, lung function, symptom scores, and serum C-reactive protein were assessed. MEASUREMENTS AND MAIN RESULTS: On Day 30, clinical success was similar in intention-to-treat patients (odds ratio, 1.3; 95% confidence interval, 0.8 to 2.0) and per-protocol patients. Doxycycline showed superiority over placebo in terms of clinical success on Day 10 in intention-to-treat patients (odds ratio, 1.9; 95% confidence interval, 1.1 to 3.2), but not in per-protocol patients. Doxycycline was also superior in terms of clinical cure on Day 10, microbiological outcome, use of open label antibiotics, and symptoms. There was no interaction between the treatment effect and any of the subgroup variables (lung function, type of exacerbation, serum C-reactive protein, and bacterial presence). CONCLUSIONS: Although equivalent to placebo in terms of clinical success on Day 30, doxycycline showed superiority in terms of clinical success and clinical cure on Day 10, microbiological success, the use of open label antibiotics, and symptoms. Clinical trial registered with www.clinicaltrials.gov (NCT00170222).
Authors: David Gillespie; Christopher C Butler; Janine Bates; Kerenza Hood; Hasse Melbye; Rhiannon Phillips; Helen Stanton; Mohammed Fasihul Alam; Jochen Wl Cals; Ann Cochrane; Nigel Kirby; Carl Llor; Rachel Lowe; Gurudutt Naik; Evgenia Riga; Bernadette Sewell; Emma Thomas-Jones; Patrick White; Nick A Francis Journal: Br J Gen Pract Date: 2021-03-26 Impact factor: 5.386
Authors: Nick A Francis; David Gillespie; Patrick White; Janine Bates; Rachel Lowe; Bernadette Sewell; Rhiannon Phillips; Helen Stanton; Nigel Kirby; Mandy Wootton; Emma Thomas-Jones; Kerenza Hood; Carl Llor; Jochen Cals; Hasse Melbye; Gurudutt Naik; Micaela Gal; Deborah Fitzsimmons; Mohammed Fasihul Alam; Evgenia Riga; Ann Cochrane; Christopher C Butler Journal: Health Technol Assess Date: 2020-03 Impact factor: 4.014