Oral Nalbuphine in Idiopathic Pulmonary Fibrosis-Associated Cough: The CORAL Randomized Clinical Trial

# Oral Nalbuphine in Idiopathic Pulmonary Fibrosis-Associated Cough: The CORAL Randomized Clinical Trial *Published: 2026 Mar 24* reported receiving nonfinancial support from Trevi Therapeutics during the conduct of the study; grants from AstraZeneca, GSK, and Boehringer Ingelheim; and personal fees from AstraZeneca, Calluna Pharma, Contineum Therapeutics, GSK, Gossamer Bio, Puretech, Qureight, Redx, Vicore Pharma, Trevi Therapeutics, and Boehringer Ingelheim outside the submitted work. Dr Kreuter reported receiving personal fees from Boehringer Ingelheim, AstraZeneca, Chiesi, Trevi Therapeutics, GSK, Pliant, and Bristol Myers Squibb outside the submitted work. Dr Neustifter reported receiving personal fees from Trevi Therapeutics for statistical consultation via Alimentiv during the conduct of the study. Dr Mathur reported receiving personal fees from Trevi Therapeutics during the conduct of the study. Dr Cassella reported being an employee of and owning stock in Trevi Therapeutics during the conduct of the study. No other disclosures were reported. 17. JAMA. 2026 Mar 24;335(12):1041-1049. doi: 10.1001/jama.2025.25921. Antibiotic Therapy for Uncomplicated Acute Appendicitis: Ten-Year Follow-Up of the APPAC Randomized Clinical Trial. Salminen P(1)(2), Salminen R(2)(3), Kallio J(4), Hurme S(1)(5), Nordström P(6), Rantanen T(7)(8), Paajanen H(9), Aarnio M(10), Mecklin JP(10), Sand J(6), Grönroos JM(1)(2), Rautio T(3). Author information: (1)Division of Digestive Surgery and Urology, Turku University Hospital, Turku, Finland. (2)Department of Surgery, University of Turku, Turku, Finland. (3)Oulu University Hospital and Medical Research Center Oulu, University of Oulu, Oulu, Finland. (4)Department of Radiology, Turku University Hospital, Turku, Finland. (5)Department of Biostatistics, University of Turku and Turku University Hospital, Turku, Finland. (6)Division of Surgery, Gastroenterology and Oncology, Tampere University Hospital, Tampere, Finland. (7)Department of Surgery, Kuopio University Hospital, Kuopio, Finland. (8)Department of Surgery, Institute of Clinical Medicine, University of Eastern Finland, Kuopio, Finland. (9)Department of Surgery, Mikkeli Central Hospital, Mikkeli, Finland. (10)Department of Education and Research, Wellbeing Services County of Central Finland, Jyväskylä, Finland. Comment in JAMA. 2026 Mar 24;335(12):1039-1040. doi: 10.1001/jama.2025.26612. ## IMPORTANCE Antibiotic therapy is effective and safe for uncomplicated acute appendicitis in adults, but randomized clinical trial results exceeding 5 years are missing. ## OBJECTIVE To determine the 10-year appendicitis recurrence and appendectomy rate in patients with uncomplicated appendicitis treated with antibiotics. DESIGN, SETTING, AND PARTICIPANTS Ten-year observational follow-up of patients in the Appendicitis Acuta (APPAC) multicenter randomized clinical trial comparing appendectomy with antibiotics at 6 Finnish hospitals from November 2009 to June 2012, where 530 patients (aged 18-60 years) with uncomplicated acute appendicitis diagnosed by computed tomography were randomly assigned to appendectomy (n = 273) or antibiotics (n = 257). Last follow-up was April 29, 2024. This current analysis focused on assessing the 10-year appendicitis recurrence rate among patients assigned to antibiotics. ## INTERVENTIONS Open appendectomy vs antibiotics with intravenous ertapenem sodium (1 g/d) for 3 days followed by 7 days of oral levofloxacin (500 mg once daily) and metronidazole (500 mg 3 times/d). MAIN OUTCOMES AND MEASURES Prespecified 10-year secondary end points included late (after 1 year) appendectomy and appendicitis recurrence rate after antibiotics and complications. Post hoc outcomes included the detection of possible appendiceal tumors among patients in the antibiotic group undergoing appendectomy or with an intact appendix using magnetic resonance imaging. Additional post hoc outcomes were quality of life and patient satisfaction. ## RESULTS At 10-year follow-up, 253/257 patients (98.4%) randomized to receive antibiotics (median age, 33 years; 102 [40.3%] female) were assessed for appendicitis recurrence, with a true appendicitis recurrence rate (appendicitis at histopathology) of 37.8% (95% CI, 31.6%-44.1% [87/230]) and a cumulative appendectomy rate of 44.3% (95% CI, 38.2%-50.4% [112/253]). Overall, the 10-year cumulative complication rate in the group randomized to appendectomy was 27.4% (95% CI, 21.6%-33.3% [62/226]) and 8.5% (95% CI, 4.8%-12.1% [19/224]) in the group randomized to receive antibiotics (P < .001). There was no observed significant difference in quality of life between antibiotics and appendectomy (387/530; median health index value, 1.0 [95% CI, 1.0-1.0] for both groups; P = .18). CONCLUSIONS AND RELEVANCE Among patients initially treated with antibiotics for uncomplicated acute appendicitis, the rate of recurrence and appendectomy at 10-year follow-up supports the use of antibiotics as an option for uncomplicated acute appendicitis in adult patients. ## TRIAL REGISTRATION ClinicalTrials.gov Identifier: NCT01022567. DOI: 10.1001/jama.2025.25921 PMCID: PMC12824850 DOI: 10.1001/jama.2025.26179