Randomized adaptive assessment of post COVID syndrome treatments (RAPID): a study protocol for a multicenter, randomized, controlled adaptive platform trial of treatment options for Post Covid Syndrome (PCS) on patients physical function including the first intervention specific appendix RAPID_REVIVE (reducing inflammatory activity in patients with PCS).

Ralph G Telgmann, Maria Vehreschild, Heike Valentin, Ralf Tostmann, Ann-Cathrin Schmidt, Jens Schaller, Dagmar Krefting, Monika Kraus, Cynthia Huber, Sabine Hanß, Julia Groth, Sonja Drescher, Irina Chaplinskaja-Sobol, Gabriele Anton, Birgit Sawitzki, Lisa Weipert, Thomas Asendorf, Matthias Nauck, Wolfgang Hoffmann, Thomas Illig, Sandra Ciesek, Oliver A Cornely, Tim Friede, Sebastian Kuhn, Carsten Finke, Andreas Muehler, Georg Schmidt

Journal: Trials 2025;26(1):297

PMID: 40830806

Free Full Text on BioMed Central View on PubMed

Abstract

BACKGROUND

The majority of patients recovers from severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2) coronavirus disease 2019 (COVID-19) without obvious sequelae, but a significant proportion suffers long-term consequences which have been termed post COVID syndrome (PCS). Despite a wide range of considerations on treatment options in PCS and a significant number of trials initiated, only very few results from randomized controlled trials are currently available. In conclusion, there is an evident medical need to identify treatments for patients with PCS.

METHODS

The primary objective of the platform trial RAPID is to assess the impact of different PCS treatments on the overall physical function of patients. Designed as a master protocol, RAPID contains all information that is generic to this adaptive platform trial. Current and future study treatments are specified in intervention-specific appendices (ISA). The first ISA, RAPID_REVIVE is presented in this manuscript. General sections of the master protocol are named as such. RAPID_REVIVE is a double-blind, placebo-controlled, phase II clinical trial evaluating antiviral PCS treatment with vidofludimus calcium (IMU-838). Patients are randomized at a 1:1 ratio to 45 mg/day vidofludimus calcium (22.5 mg for the first 7 days) or placebo during an initialization phase and thereafter using a response-adaptive randomization procedure. The trial includes a screening period of 7 days, a double-blind treatment period of 56 days and a follow-up period of 28 days. The primary outcome is the intra-patient change in physical function measured by the Short Form-36 Physical Function (SF-36-PF) from baseline to day 56. Secondary endpoints include mental and physical health, intensity of fatigue, severity of mental disorder symptoms, and cognitive function.

DISCUSSION

PCS is a major problem for global health care and the identification of treatment options is urgently needed. Currently, PCS patients are in a situation without evidence-based treatment options, and quality of life, and often mental health are significantly impaired. The purpose of RAPID is to establish an adaptive platform trial protocol which will concert and quicken clinical trials to evaluate the efficacy and safety of different potential treatments for PCS with the aim to expand the very limited evidence base for the treatment of PCS.

TRIAL REGISTRATION

EU Clinical Trials Register (CTIS) ID: 2024-511628-16-00 (RAPID_REVIVE). Registered on 18.03.2024.

Address: Department II of Internal Medicine, Infectious Diseases, Goethe University Frankfurt, University Hospital Frankfurt, Frankfurt am Main, Germany.; Clinical Trials Unit, University Medical Center Göttingen, Göttingen, Germany.; Medical School OWL, Bielefeld University, Bielefeld, Germany.; Department of Medical Statistics, University Medical Center Göttingen, Göttingen, Germany.; University Medical Center Göttingen, Department of Medical Informatics, Göttingen, Germany.; Institute for Medical Virology, University Hospital Frankfurt, Goethe University Frankfurt, Frankfurt, Germany.; University of Cologne, Faculty of Medicine, University Hospital Cologne, Institute of Translational Research, Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECA), Cologne, Germany.; University of Cologne, Faculty of Medicine, University Hospital Cologne, Department I of Internal Medicine, Center for Integrated Oncology Aachen Bonn Cologne Duesseldorf (CIO ABCD) and Excellence Center for Medical Mycology (ECMM), Cologne, Germany.; German Centre for Infection Research (DZIF), Partner Site Bonn-Cologne, Cologne, Germany.; University of Cologne, Faculty of Medicine, University Hospital Cologne, Clinical Trials Centre Cologne (ZKS Köln), Cologne, Germany.; Department of Neurology, Charité, University Medicine Berlin, Berlin, Germany, Berlin School of Mind and Brain, Humboldt-Universität zu Berlin, Berlin, Germany.; Helmholtz Centre Munich, Institute of Epidemiology, Department of Molecular Epidemiology, Munich, Germany.; Institute of Community Medicine, Department of Healthcare Epidemiology and Community Health, University Medicine Greifswald, Greifswald, Germany.; Hannover Medical School, Hannover Unified Biobank, Hannover, Germany.; Institute for Digital Medicine, University Hospital Giessen-Marburg, Philipps University Marburg, Marburg, Germany.; Immunic AG, Lochhamer Schlag 21, Gräfelfing, 82166, Germany.; Institute for Clinical Chemistry and Laboratory Medicine, University Medicine Greifswald, Greifswald, Germany.; Institute for Cardiovascular Computer-Assisted Medicine, Charité, University Medicine Berlin, Berlin, Germany.; Klinikum rechts der Isar, Technical University of Munich, Munich, Germany.; Institute of Medical Immunology, Charité, University Medicine Berlin, Berlin, Germany.; Department II of Internal Medicine, Infectious Diseases, Goethe University Frankfurt, University Hospital Frankfurt, Frankfurt am Main, Germany. [email protected].

DOI: 10.1186/s13063-025-09008-0

Link outs

Free resources

Full Text Sources:

Medical:

https://medlineplus.gov/covid19coronavirusdisease2...

Miscellaneous:

https://assays.cancer.gov/CPTAC-438

MeSH Terms: Humans, Adaptive Clinical Trials as Topic, COVID-19, Multicenter Studies as Topic, Post-Acute COVID-19 Syndrome, Randomized Controlled Trials as Topic, Treatment Outcome