Safety and efficacy of faecal microbiota transplantation by Anaerobic Cultivated Human Intestinal Microbiome (ACHIM) in patients with systemic sclerosis: study protocol for the randomised controlled phase II ReSScue trial.

INTRODUCTION: In the multisystem inflammatory disorder systemic sclerosis (SSc), gastrointestinal tract (GIT) affliction is highly prevalent. There are no known disease modifying therapies and the negative impact is substantial. Aiming for a new therapeutic principle, and inspired by recent work showing associations between gut microbiota changes and GIT symptoms in SSc, we performed a pilot study on faecal microbiota transplantation (FMT) with the single-donor bacterial culture 'Anaerobic Cultivated Human Intestinal Microbiome (ACHIM)'. Motivated by positive pilot study signals, we designed the ReSScue trial as a phase II multicentre, placebo-controlled, randomised 20-week trial to evaluate safety and efficacy on lower GIT symptoms of FMT by ACHIM in SSc. METHODS AND ANALYSES: We aim to include 70 SSc participants with moderate to severe lower GIT symptoms, defined by the validated patient-reported University of California Los Angeles Scleroderma Clinical Trial Consortium GIT 2.0 2.0 questionnaire. The trial includes three parts. In part A1 (induction phase) lasting from week 0 to week 12, participants will be randomised 1:1 to repeat infusions of 30 mL ACHIM or placebo at week 0 and 2 by gastroduodenoscopy. In part A2, which is an 8-week subsequent maintenance phase, all study participants will receive 30 mL ACHIM at week 12 and followed until week 20 on continued blind. In part B, which will last until the last participant completes part A2, the participants will be followed through a maximum 16-week extended monitoring period, for longer-term data on safety and intervention effects. Primary endpoint is change from baseline to week 12 in UCLA GIT subscale scores of diarrhoea or bloating, depending on the worst symptom at baseline evaluated separately for each patient. Secondary endpoints are safety measures and changes in UCLA GIT scores (total, diarrhoea and bloating). ETHICS AND DISSEMINATION: This protocol was approved by the Northern Norwegian Committee for Medical Ethics. Study findings will be published. TRIAL REGISTRATION NUMBER: NCT04300426; Pre-results. PROTOCOL VERSION: V.3.1.

Are patients with COPD treated with NIV in accordance with national guidelines? An internal audit.

INTRODUCTION: Non-invasive ventilation (NIV) as an add-on modality to medical treatment has been recommended in national guidelines for patients acutely admitted with chronic obstructive pulmonary disorder (COPD) exacerbation and hypercapnic respiratory failure. To address concerns regarding whether NIV is used appropriately, we conducted an audit of COPD patients admitted to a university hospital in Denmark. MATERIAL AND METHODS: Data from medical records were retrieved for two cohorts in 2010: 1) all patients admitted to the Medical Emergency Ward with the diagnosis of COPD, and 2) all patients receiving NIV regardless of their diagnosis at the Respiratory Ward. Demographic data and outcome of treatment were registered. RESULTS: Cohort 1 comprised 804 admissions fulfilling criteria for COPD at evaluation, and of the 804 admissions, NIV was initiated in 151 (18.7%) admissions. In 42 additional cases (5.2%), initial mild respiratory acidosis was registered at admission, fulfilling criteria for NIV treatment; and, in 36 cases, the clinical status was reported as improved or not reported at all; no deaths were observed. In cohort 2, 124 admissions were registered that comprised 110 admissions with COPD and 14 without a diagnosis of COPD (of which half had a 'not-to-intubate' order). The indication for NIV treatment was met in 92.7% of the COPD admissions. CONCLUSION: NIV was initiated in 18.8% of the COPD admissions, and in an additional 5.2%, NIV criteria were met without initiation. In 82.3% of the admissions receiving NIV, a COPD diagnosis and correct criteria for NIV treatment were met.