Standardized Treatment of Pulmonary Exacerbations II

The study will assess the non-inferiority of 10 days versus 14 days treatment duration among patients who have an early robust improvement (ERR subjects) and the superiority of 21 days versus 14 days treatment duration among the subjects who do not meet the definition of ERR (non-ERR; NERR).

Subjects will undergo pulmonary function testing (spirometry) and complete a respiratory symptom score [Chronic Respiratory Infection Symptom Score (CRISS)] at initiation of IV treatment (Baseline/ Visit 1) and at Day 7-10 (Visit 2). At Visit 2, subjects will be allocated to groups ERR or NERR based on their initial clinical response as determined by the change in forced expiratory volume in 1 second (FEV1; percent of predicted) and CRISS from Baseline and then randomized to an IV treatment duration (nested within group).

ERR subjects [≥8% predicted improvement in FEV1 from Visit 1 to Visit 2 and CRISS reduction of ≥11 points from Visit 1 to Visit 2] will be randomized 1:1 to either 10 days or 14 days total IV antibiotic treatment duration. Remaining (NERR) subjects will be randomized 1:1 to receive either 14 or 21 days total IV antibiotic treatment duration. All subjects will be evaluated again at Visit 3, 14 days following scheduled completion of IV antibiotic treatment.

Inclusion criteria

Key Inclusion Criteria:

• Male or female ≥18 years of age at Visit 1
• Documentation of a CF diagnosis
• Enrolled in the Cystic Fibrosis Foundation National Patient Registry (CFFNPR) prior to Visit 1 (US sites only)
• At the time of Visit 1, there is a plan to initiate IV antibiotics for a pulmonary exacerbation
• Performed spirometry at Visit 1 and Visit 2 and willing to perform spirometry at Visit 3
• Completed the CRISS questionnaire at Visit 1 and Visit 2 and willing to complete the Cystic Fibrosis Respiratory Symptoms Diary (CFRSD) questionnaire at Visit 3
• Willing to adhere to a specific treatment duration determined by initial response to treatment and subsequent randomization
• Willing to return for follow up Visit 3
• Written informed consent obtained from the subject or subject's legal representative

Exclusion criteria

Key Exclusion Criteria

• Previous randomization in this study
• Treatment with IV antibiotics in the 6 weeks prior to Visit 1
• Admission to the intensive care unit for current pulmonary exacerbation in the two weeks prior to Visit 2, unless admission was due to a desensitization protocol
• Pneumothorax in the two weeks prior to Visit 2
• Primary diagnosis for current hospitalization is unrelated to worsening lower respiratory symptoms (e.g., pulmonary clean out, distal intestinal obstruction syndrome (DIOS), sinusitis)
• Massive hemoptysis defined as > 250 cc in a 24 hour period or 100 cc/day over 4 consecutive days occurring in the two weeks prior to Visit 2
• Current pulmonary exacerbation thought to be due to allergic bronchopulmonary aspergillosis (ABPA)
• At Visit 1, receiving ongoing treatment with a duration of more than 2 weeks with prednisone equivalent to >10mg/day
• History of solid organ transplantation
• Receiving antimicrobial therapy to treat non-tuberculous mycobacterium (e.g., M. abscessus, M. avium complex) in the two weeks prior to Visit 2