The RECLAIM adaptive platform trial for the evaluation of treatments for post-COVID condition in the Netherlands: core protocol.
Post-COVID condition (PCC) encompasses a heterogeneous spectrum of pathological responses to SARS-CoV-2 infection, with unknown individual predispositions. No evidence-based, curative treatments are available. Many patients therefore resort to off-label use of medications originally developed for other indications. However, the efficacy and safety of repurposed drugs in the context of PCC are unknown.
RECLAIM is a phase III, randomised, controlled, adaptive platform trial. The trial population consists of adult patients who have had persistent PCC symptoms, including fatigue and/or post-exertional malaise, 12 or more weeks after the onset of a SARS-CoV-2 infection. Randomisation occurs within trial domains. A trial domain consists of one or multiple investigational products (IPs), each to be compared to one usual care arm, or one or multiple IPs, each to be compared to a matching placebo. Within each trial domain, patients can be enrolled if they are eligible for at least one IP and its control. They are randomised with equal probability to each arm for which they are eligible. Trial product use (if applicable) starts as soon as possible after randomisation for a default duration of 12 weeks. Study procedures are implemented remotely, using video consultations, eConsenting, trial product delivery to participants' homes (if applicable), and online questionnaires at baseline, day 1, and weeks 2, 4, 6, 8, 10, 12, and 24. The primary outcome is health-related quality of life at week 12, assessed by Patient-Reported Outcomes Measurement Information System Profile29 (PROMIS-29) physical health summary scores, and is analysed with a Bayesian analysis of covariance model with adjustment for the baseline value. Secondary outcomes include week 12 PROMIS-29 mental health summary scores and topic domain scores; specific PCC symptoms using other patient-reported outcome measures, safety, and tolerability; and durability of treatment responses at week 24. Participants are allowed to participate in only one trial domain at a time, but can be rerandomised into a different trial domain after completing week 24.
RECLAIM commenced in February 2025 with an open-label domain including two IP arms (metformin and colchicine) and one usual care control arm. A second placebo-controlled domain, comparing minocycline to a matching placebo, was initiated in February 2026.
European Clinical Trials Information System (CTIS) EUCT number 2024-511580-28-02. Registered on 9 October 2024.
gov identifier NCT07280572. Registered on 11 December 2025.
RECLAIM is a phase III, randomised, controlled, adaptive platform trial. The trial population consists of adult patients who have had persistent PCC symptoms, including fatigue and/or post-exertional malaise, 12 or more weeks after the onset of a SARS-CoV-2 infection. Randomisation occurs within trial domains. A trial domain consists of one or multiple investigational products (IPs), each to be compared to one usual care arm, or one or multiple IPs, each to be compared to a matching placebo. Within each trial domain, patients can be enrolled if they are eligible for at least one IP and its control. They are randomised with equal probability to each arm for which they are eligible. Trial product use (if applicable) starts as soon as possible after randomisation for a default duration of 12 weeks. Study procedures are implemented remotely, using video consultations, eConsenting, trial product delivery to participants' homes (if applicable), and online questionnaires at baseline, day 1, and weeks 2, 4, 6, 8, 10, 12, and 24. The primary outcome is health-related quality of life at week 12, assessed by Patient-Reported Outcomes Measurement Information System Profile29 (PROMIS-29) physical health summary scores, and is analysed with a Bayesian analysis of covariance model with adjustment for the baseline value. Secondary outcomes include week 12 PROMIS-29 mental health summary scores and topic domain scores; specific PCC symptoms using other patient-reported outcome measures, safety, and tolerability; and durability of treatment responses at week 24. Participants are allowed to participate in only one trial domain at a time, but can be rerandomised into a different trial domain after completing week 24.
RECLAIM commenced in February 2025 with an open-label domain including two IP arms (metformin and colchicine) and one usual care control arm. A second placebo-controlled domain, comparing minocycline to a matching placebo, was initiated in February 2026.
European Clinical Trials Information System (CTIS) EUCT number 2024-511580-28-02. Registered on 9 October 2024.
gov identifier NCT07280572. Registered on 11 December 2025.
Authors
van de Wijgert van de Wijgert, Schoevers Schoevers, Swarthout Swarthout, Bouwman Bouwman, van Rosmalen van Rosmalen, Leffelaar Leffelaar, Lalmohamed Lalmohamed, Loch Loch, van den Wijngaard van den Wijngaard, Prat-Aymerich Prat-Aymerich, Schotsman Schotsman, Verheijen Verheijen, van der Bom van der Bom, Bonten Bonten
View on Pubmed