Active substances: Doxycycline
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Aliquots of cells and medium were removed at 2-day intervals. The absorbance of the DNA solution at 260 and 280 nm was determined by spectrophotometry.
The gels were stained with ethidium bromide and then photographed. Supernatants containing the viruses were harvested 48 h later, and filtered supernatants were used to infect cells.
Puromycin-resistant cells were pooled for subsequent analysis. The trial will randomize approximately 500 individuals in a 1:1 ratio to either antimicrobial therapy or usual care.
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. Background IPF is a chronic, fibrotic, and progressive interstitial lung disease characterized by the histopathologic pattern of usual interstitial pneumonia in the absence of an identifiable cause or association.
Disease progression is highly heterogeneous with a median survival of approximately 3—5 years following diagnosis.
Furthermore, the increasing rate of mortality and hospitalization related to the disease suggests that the prevalence is increasing. Studies of pirfenidone and nintedanib have shown consistent beneficial effects in forced vital capacity and led to approval of both agents by the U.
As a result, there remains an unmet clinical need for effective and low cost treatment strategies to improve the quality-of-life and clinical outcomes in patients with IPF.
Methods What is the rationale for the antimicrobial therapies?
Compelling data have linked disease progression with lung dysbiosis and the resulting local and systemic immune response in IPF patients.
Murine data support the impact of lung microbes on increased fibrotic response.
In other chronic disorders, antimicrobial therapy has been suggested to favorably alter the lung microbial community. This trial utilizes a pragmatic approach with antimicrobial agents that have been suggested to have a similar effect in IPF patients.
The use of two potentially effective therapies minimizes potential risk while increasing the number of patients that can be treated with such innovative therapy. What is the rationale for using co-trimoxazole?
An initial randomized trial of 20 patients with advanced fibrotic lung disease showed favorable improved exercise capacity and symptom scores in the participants assigned to co-trimoxazole.
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