Randomized controlled phase 2 trial of hydroxychloroquine in childhood interstitial lung disease

Orphanet Journal of Rare Diseases

Research

Hans Rock¹  Nicolaus Schwerk²  Martin Wetzke²  Julia Carlens²  Lutz Nährlich³  Matthias Kappler⁴  Matthias Griese⁴  Daniela Sebah⁴  Elias Seidl⁴  Kai Kronfeld⁵  Christian Ruckes⁵  Freerk Prenzel⁶  Andreas Thalmeier⁷  Florian Stehling⁸  Winfried Baden⁹  Cordula Koerner-Rettberg^1,10  Johannes Schulze^1,11 

[1] Central Information Office GmbH, Fronhausen, Bellnhausen, Germany;Department of Paediatric Pneumonology, Allergology and Neonatology, Hannover Medical School, German Center for Lung Research (DZL), Hannover, Germany;Department of Pediatrics, Justus-Liebig-University Giessen, German Center for Lung Research, Universities of Giessen and Marburg Lung Center (UGMLC), Giessen, Germany;Dr. von Hauner Children´s Hospital, University of Munich, German Center for Lung Research (DZL), Lindwurmstraße 4, 80337, Munich, Germany;IZKS, Interdisciplinary Center for Clinical Trials, University Medical Center Mainz, Mainz, Germany;Klinik und Poliklinik für Kinder- und Jugendmedizin der Universität Leipzig, Liebigstraße 20a, Haus 6, 04103, Leipzig, Germany;Pharmacy, University Hospital of Munich, Munich, Germany;Uniklinikum Essen Pädiatrische Pneumologie, Kinderheilkunde III, Hufelandstr. 55, 45122, Essen, Germany;Universitätsklinik für Kinder- und Jugendmedizin Tübingen, Hoppe-Seyler-Str. 1, 72076, Tübingen, Germany;Universitätsklinik für Kinder- und Jugendmedizin im St. Josef-Hospital Bochum, Alexandrinenstraße 5, 44791, Bochum, Germany;Universitätsklinikum Frankfurt Klinik für Kinder- und Jugendmedizin, Pneumologie, Allergologie and Mukoviszidose, Theodor-Stern-Kai 7, 60590, Frankfurt, Germany;

关键词: chILD;    Interstitial lung diseases;    Hydroxychloroquine;    Randomized-controlled trial;   

DOI  :  10.1186/s13023-022-02399-2

 received in 2022-04-24, accepted in 2022-06-11,  发布年份 2022

来源: Springer

【 摘 要 】

BackgroundNo results of controlled trials are available for any of the few treatments offered to children with interstitial lung diseases (chILD). We evaluated hydroxychloroquine (HCQ) in a phase 2, prospective, multicentre, 1:1-randomized, double-blind, placebo-controlled, parallel-group/crossover trial. HCQ (START arm) or placebo were given for 4 weeks. Then all subjects received HCQ for another 4 weeks. In the STOP arm subjects already taking HCQ were randomized to 12 weeks of HCQ or placebo (= withdrawal of HCQ). Then all subjects stopped treatment and were observed for another 12 weeks.Results26 subjects were included in the START arm, 9 in the STOP arm, of these four subjects participated in both arms. The primary endpoint, presence or absence of a response to treatment, assessed as oxygenation (calculated from a change in transcutaneous O2-saturation of ≥ 5%, respiratory rate ≥ 20% or level of respiratory support), did not differ between placebo and HCQ groups. Secondary endpoints including change of O2-saturation ≥ 3%, health related quality of life, pulmonary function and 6-min-walk-test distance, were not different between groups. Finally combining all placebo and all HCQ treatment periods did not identify significant treatment effects. Overall effect sizes were small. HCQ was well tolerated, adverse events were not different between placebo and HCQ.ConclusionsAcknowledging important shortcomings of the study, including a small study population, the treatment duration, lack of outcomes like lung function testing below age of 6 years, the small effect size of HCQ treatment observed requires careful reassessments of prescriptions in everyday practice (EudraCT-Nr.: 2013-003714-40, www.clinicaltrialsregister.eu, registered 02.07.2013).Registration The study was registered on 2 July 2013 (Eudra-CT Number: 2013-003714-40), whereas the approval by BfArM was received 24.11.2014, followed by the approval by the lead EC of the University Hospital Munich on 20.01.2015. At clinicaltrials.gov the trial was additionally registered on November 8, 2015 (NCT02615938).

【 授权许可】

CC BY   
© The Author(s) 2022. corrected publication 2023

【 图 表 】

Fig. 4