Sonya L Heltshe1, Natalie E West2, Donald R VanDevanter3, D B Sanders4, Valeria V Beckett5, Patrick A Flume6, Christopher H Goss7. 1. CFF Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle, WA 98121, USA; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA. Electronic address: sonya.heltshe@seattlechildrens.org. 2. Division of Pulmonary and Critical Care Medicine, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. 3. Case Western Reserve University School of Medicine, Cleveland, OH 44106, USA. 4. Department of Pediatrics, Riley Hospital for Children, School of Medicine, Indiana University, Indiana, IN 46202, USA. 5. CFF Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle, WA 98121, USA. 6. Departments of Medicine and Pediatrics, Medical University of South Carolina, Charleston, SC 29425, USA. 7. CFF Therapeutics Development Network Coordinating Center, Seattle Children's Research Institute, Seattle, WA 98121, USA; Department of Pediatrics, University of Washington School of Medicine, Seattle, WA 98195, USA; Division of Pulmonary Medicine, Department of Medicine, University of Washington School of Medicine, Seattle, WA 98121, USA.
Abstract
BACKGROUND: Pulmonary exacerbations (PEx) in cystic fibrosis (CF) are common and contribute to morbidity and mortality. Duration of IV antibiotic therapy to treat PEx varies widely in the US, and there are few data to guide treatment decisions. METHODS: We combined a survey of CF stakeholders with retrospective analyses of a recent observational study of CF PEx to design a multicenter, randomized, prospective study comparing the efficacy and safety of different durations of IV antibiotics for PEx to meet the needs of people with CF and their caregivers. RESULTS: IV antibiotic duration was cited as the most important PEx research question by responding CF physicians and top concern among surveyed CF patients/caregivers. During PEx, forced expiratory volume in 1s (FEV1% predicted) and symptom responses at 7-10days of IV antibiotics identified two distinct groups: early robust responders (ERR) who subsequently experienced greater FEV1 improvements compared to non-ERR (NERR). In addition to greater FEV1 and symptom responses, only 14% of ERR patients were treated with IV antibiotics for >15days, compared with 45% of NERR patients. CONCLUSIONS: A divergent trial design that evaluates subjects' interim improvement in FEV1 and symptoms to tailor randomization to IV treatment duration (10 vs. 14days for ERR, 14 vs. 21days for NERR) may alleviate physician and patient concerns about excess or inadequate treatment. Such a study has the potential to provide evidence necessary to standardize IV antibiotic duration in CF PEx care -a first step to conducting PEx research of other treatment features.
RCT Entities:
BACKGROUND: Pulmonary exacerbations (PEx) in cystic fibrosis (CF) are common and contribute to morbidity and mortality. Duration of IV antibiotic therapy to treat PEx varies widely in the US, and there are few data to guide treatment decisions. METHODS: We combined a survey of CF stakeholders with retrospective analyses of a recent observational study of CF PEx to design a multicenter, randomized, prospective study comparing the efficacy and safety of different durations of IV antibiotics for PEx to meet the needs of people with CF and their caregivers. RESULTS: IV antibiotic duration was cited as the most important PEx research question by responding CF physicians and top concern among surveyed CF patients/caregivers. During PEx, forced expiratory volume in 1s (FEV1% predicted) and symptom responses at 7-10days of IV antibiotics identified two distinct groups: early robust responders (ERR) who subsequently experienced greater FEV1 improvements compared to non-ERR (NERR). In addition to greater FEV1 and symptom responses, only 14% of ERR patients were treated with IV antibiotics for >15days, compared with 45% of NERR patients. CONCLUSIONS: A divergent trial design that evaluates subjects' interim improvement in FEV1 and symptoms to tailor randomization to IV treatment duration (10 vs. 14days for ERR, 14 vs. 21days for NERR) may alleviate physician and patient concerns about excess or inadequate treatment. Such a study has the potential to provide evidence necessary to standardize IV antibiotic duration in CF PEx care -a first step to conducting PEx research of other treatment features.
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