Clean-UP IPF

Clean-UP IPF was the first pragmatic trial in IPF that studied whether antimicrobial therapy would improve hospitalization or decrease death. Pragmatic trials are aimed at evaluating the effectiveness of treatments in real-life settings. 

The study was a collaboration with the National Heart, Lung, and Blood Institute (NHLBI), several philanthropic organizations, and a broad investigative community. The study was completed on October 31, 2020 and published in the May 2021 issue of the Journal of the American Medical Association (JAMA): “Effect of antimicrobial therapy on respiratory hospitalization or death in adults with idiopathic pulmonary fibrosis: The CleanUP-IPF Randomized Clinical Trial”.

The PDF can be found by clicking here. 

Additional information:

dcri.org

Randomized, Pragmatic Trial Testing Antimicrobial Therapy for Treatment of Idiopathic Pulmonary Fibrosis Shows No Significant Effect

A large pragmatic study in idiopathic pulmonary fibrosis (IPF) found that antimicrobial therapy did not have a statistically significant effect on respiratory hospitalization or death compared with usual care alone.

“Comparison of Pirfenidone and Nintedanib: Post Hoc Analysis of the Clean-UP-IPF

Study” published in CHEST. Reference

“Design and rationale of a multi-center, pragmatic, open-label randomized trial of

antimicrobial therapy – the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial” published in Respiratory Research.

respiratory-research.biomedcentral.com

Design and rationale of a multi-center, pragmatic, open-label randomized trial of antimicrobial therapy – the study of clinical efficacy of antimicrobial therapy strategy using pragmatic design in Idiopathic Pulmonary Fibrosis (CleanUP-IPF) clinical trial - Respiratory Research

Abstract Compelling data have linked disease progression in patients with idiopathic pulmonary fibrosis (IPF) with lung dysbiosis and the resulting dysregulated local and systemic immune response. Moreover, prior therapeutic trials have suggested improved outcomes in these patients treated with either sulfamethoxazole/ trimethoprim or doxycycline. These trials have been limited by methodological concerns. This trial addresses the primary hypothesis that long-term treatment with antimicrobial therapy increases the time-to-event endpoint of respiratory hospitalization or all-cause mortality compared to usual care treatment in patients with IPF. We invoke numerous innovative features to achieve this goal, including: 1) utilizing a pragmatic randomized trial design; 2) collecting targeted biological samples to allow future exploration of ‘personalized’ therapy; and 3) developing a strong partnership between the NHLBI, a broad range of investigators, industry, and philanthropic organizations. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care. The site principal investigator will declare their preferred initial antimicrobial treatment strategy (trimethoprim 160 mg/ sulfamethoxazole 800 mg twice a day plus folic acid 5 mg daily or doxycycline 100 mg once daily if body weight is < 50 kg or 100 mg twice daily if ≥50 kg) for the participant prior to randomization. Participants randomized to antimicrobial therapy will receive a voucher to help cover the additional prescription drug costs. Additionally, those participants will have 4–5 scheduled blood draws over the initial 24 months of therapy for safety monitoring. Blood sampling for DNA sequencing and genome wide transcriptomics will be collected before therapy. Blood sampling for transcriptomics and oral and fecal swabs for determination of the microbiome communities will be collected before and after study completion. As a pragmatic study, participants in both treatment arms will have limited in-person visits with the enrolling clinical center. Visits are limited to assessments of lung function and other clinical parameters at time points prior to randomization and at months 12, 24, and 36. All participants will be followed until the study completion for the assessment of clinical endpoints related to hospitalization and mortality events. Trial Registration ClinicalTrials.gov identifier NCT02759120 .

The lead investigator was Fernando Martinez, MD, MS, the Joseph D. Early Chair in

Biomedical Research, Professor of Medicine, Vice Chair for Clinical and Translational Research, and Academic Chief of the Division of Pulmonary, Allergy, and Critical Care at UMass Chan Medical School.