Targeting Inflammation With Losartan to Improve Response to Modulator Therapy in Cystic Fibrosis.

This is a randomized, placebo-controlled, parallel group clinical trial in those those with CF on elexacaftor/tezacaftor/ivacaftor to determine if treatment with losartan improves response to modulator therapy using sweat chloride as an marker of CFTR function.

Inclusion criteria

• Established diagnosis of cystic fibrosis
• Age 12 years and older
• Stable use of elexacaftor/tezacaftor/ivacaftor for 90 days prior to enrollment
• Sweat chloride concentration 50 mmol/L or greater while on elexacaftor/tezacaftor/ivacaftor

Exclusion criteria

• Prior lung transplant
• BMI <18
• CF pulmonary exacerbation requiring hospitalization or intravenous antibiotics in the preceding 30 days
• Systemic corticosteroid or regular non-steroidal anti-inflammatory use in the preceding 30 days
• Chronic use of angiotensin receptor blockers or angiotensin converting enzyme inhibitors
• Concomitant use of medications known to interact with losartan, including aliskiren
• Chronic renal insufficiency (creatinine clearance <45 ml/min)
• Pregnancy or lactation
• Inability or unwillingness to comply with approved contraceptive method during the study period (females of childbearing age)
• In the opinion of the investigator any severe or acute or chronic condition or laboratory abnormality that may increase the risk associated with trial participation or make the participant inappropriate for enrollment
• Participation in another interventional trial that, in the opinion of the investigator, has the potential to affect the primary outcome