Infliximab in the treatment of patients with severe COVID-19 (INFLIXCOVID): protocol for a randomised, controlled, multicentre, open-label phase II clinical study

Sina M Coldewey, Charles Neu, Frank Bloos, Philipp Baumbach, Ulrike Schumacher, Michael Bauer, Philipp Reuken, Andreas Stallmach, Sina M Coldewey, Charles Neu, Frank Bloos, Philipp Baumbach, Ulrike Schumacher, Michael Bauer, Philipp Reuken, Andreas Stallmach

Abstract

Background: Despite the intense global research endeavour to improve the treatment of patients with COVID-19, the current therapy remains insufficient, resulting in persisting high mortality. Severe cases are characterised by a systemic inflammatory reaction driven by the release of pro-inflammatory cytokines such as IL-6 and tumour-necrosis-factor alpha (TNF-α). TNF-α-blocking therapies have proved beneficial in patients with chronic inflammatory diseases and could therefore pose a new treatment option in COVID-19. Hitherto, no results from randomised controlled trials assessing the effectiveness and safety of infliximab-a monoclonal antibody targeting TNF-α-in the treatment of COVID-19 have been published.

Methods: In this phase-2 clinical trial, patients with COVID-19 and clinical and laboratory signs of hyperinflammation will be randomised to receive either one dose of infliximab (5 mg/kg body weight) in addition to the standard of care or the standard of care alone. The primary endpoint is the difference in 28-day mortality. Further assessments concern the safety of infliximab therapy in COVID-19 and the influence of infliximab on morbidity and the course of the disease. For the supplementary scientific programme, blood and urine samples are collected to assess concomitant molecular changes. The Ethics Committee of the Friedrich Schiller University Jena (2021-2236-AMG-ff) and the Paul-Ehrlich-Institute (4513/01) approved the study.

Discussion: The results of this study could influence the therapy of patients with COVID-19 and affect the course of the disease worldwide, as infliximab is globally available and approved by several international drug agencies.

Trial registration: The trial was registered at clinicaltrials.gov ( NCT04922827 , 11 June 2021) and at EudraCT ( 2021-002098-25 , 19 May 2021).

Keywords: COVID-19; Infectious diseases; Molecular diagnostics; Randomised controlled trial; Respiratory infections.

Conflict of interest statement

Outside of the study, AS has received consulting fees from AbbVie, Amgen, Celltrion, Janssen, MSD, Mundipharma, and Takeda; lecture fees and support for travel accommodation from AbbVie, Amgen, FalkFoundation, Janssen, MSD, and Takeda; and research funding from Abbvie and Celltrion. All other authors declare no conflict of interest.

© 2022. The Author(s).

Figures

Fig. 1
Fig. 1
Study design. Hospitalised patients with COVID-19 (positive SARS-CoV-2 PCR testing) with pulmonary symptoms and hyperinflammation are eligible for study inclusion. Patient screening and obtainment of informed consent takes place in the general ward (S). Subsequently, patients are randomly allocated to the control (standard of care, SOC) or interventional group (SOC + infliximab) (V0). Study events take place 3 ± 1 (V1), 7 ± 1 (V2) and 14 ± 1 days after randomisation or at hospital discharge (V3). Follow-ups take place on days 28 (V4) and 90 (V5) after randomisation

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