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

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

Effect of Nintedanib on Lung Function in Patients With Systemic Sclerosis−Associated Interstitial Lung Disease: Further Analyses of a Randomized, Double‐Blind, Placebo‐Controlled Trial

none12siopenToby M. Maher, Maureen D. Mayes, Michael Kreuter, Elizabeth R. Volkmann, Martin Aringer, Ivan Castellvi, Maurizio Cutolo, Christian Stock, Nils Schoof, Margarida Alves, Ganesh Raghu, the SENSCIS Trial InvestigatorsMaher, Toby M.; Mayes, Maureen D.; Kreuter, Michael; Volkmann, Elizabeth R.; Aringer, Martin; Castellvi, Ivan; Cutolo, Maurizio; Stock, Christian; Schoof, Nils; Alves, Margarida; Raghu, Ganesh; SENSCIS Trial Investigators, Th

Feeling labeled, judged, lectured, and rejected by family and friends over depression: Cautionary results for primary care clinicians from a multi-centered, qualitative study

<p>Abstract</p> <p>Background</p> <p>Family and friends may help patients seek out and engage in depression care. However, patients’ social networks can also undermine depression treatment and recovery. In an effort to improve depression care in primary care settings, we sought to identify, categorize, and alert primary care clinicians to depression-related messages that patients hear from friends and family that patients perceive as unhelpful or detrimental.</p> <p>Methods</p> <p>We conducted 15 focus groups in 3 cities. Participants (n = 116) with a personal history or knowledge of depression responded to open-ended questions about depression, including self-perceived barriers to care-seeking. Focus group conversations were audio-recorded and analyzed using iterative qualitative analysis.</p> <p>Results</p> <p>Four themes emerged related to negatively-received depression messages delivered by family and friends. Specifically, participants perceived these messages as making them feel labeled, judged, lectured to, and rejected by family and friends when discussing depression. Some participants also expressed their interpretation of their families’ motivations for delivering the messages and described how hearing these messages affected depression care.</p> <p>Conclusions</p> <p>The richness of our results reflects the complexity of communication within depression sufferers’ social networks around this stigmatized issue. To leverage patients’ social support networks effectively in depression care, primary care clinicians should be aware of both the potentially beneficial and detrimental aspects of social support. Specifically, clinicians should consider using open-ended queries into patients’ experiences with discussing depression with family and friends as an initial step in the process. An open-ended approach may avoid future emotional trauma or stigmatization and assist patients in overcoming self-imposed barriers to depression discussion, symptom disclosure, treatment adherence and follow-up care.</p