RECLAIM Adaptive Platform Trial for PCC Treatments (RECLAIM)

RECLAIM: an Adaptive Platform Trial for the Evaluation of Treatments for Post-Acute Sequelae of SARS-CoV-2 Infection (PASC)

RECLAIM is a Phase III, multi-domain, randomized, controlled, adaptive platform trial, designed to evaluate efficacy and safety of repurposed medications in patients with post-COVID condition (PCC). The trial started in the Netherlands in February 2025, comparing metformin, colchicine and usual care in an open-label domain. The information in this registration concerns that first domain in the Netherlands. A second domain, comparing minocyclin to a matching placebo, is expected to start in January 2026, also in the Netherlands. Trial-arms, additional domains and implementing countries may be introduced or terminated as the trial progresses. Participation is fully remote, using electronic consenting, video consultations and home delivery of medication. Default IP use is 12 weeks with biweekly online follow-up questionnaires between Day-1 and Week-12, and one final follow-up questionnaire at week-24.

Study Overview

• Status: Enrolling by invitation
• Conditions: Post COVID Condition
• Intervention / Treatment: Drug: Metformin; Drug: colchicine

• Study Type: Interventional
• Enrollment (Estimated): 1250
• Phase: Phase 3

Contacts and Locations

Study Locations

• Netherlands
  • Utrecht, Netherlands
    • Julius Center for Health Sciences and Primary Care University Medical Center Utrecht, Netherlands

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

Description

Inclusion criteria

1. Adults aged 18 years or older.
2. Residing in the Netherlands (but excluding the Carribbean parts of the Netherlands) for the duration of trial participation.
3. Persistent PCC symptoms, including fatigue and/or PEM, for a period of at least 12 weeks after the onset of a SARS-CoV-2 infection. The symptoms were not present prior to the infection, but may have partially subsided and resurged after the infection.

4. Self-reported confirmation of having had a SARS-CoV-2 infection by:

   1. Positive SARS-CoV-2 nucleic acid amplification test, such as PCR;
   2. Positive SARS-CoV-2 rapid diagnostic test, including home-administered tests;
   3. COVID-19 diagnosis by a medical specialist (GP or in-hospital), based on the above or other clinical tests and assessments.

   The above information will not be verified in medical records.

5. Willing and able to provide informed consent.
6. Willing and able to perform trial procedures.
7. Allowing their GP/treating physicians/pharmacy and the RECLAIM trial team to exchange medical information that is relevant for the participant's safety and trial assessments.

Exclusion criteria:

1. Having been diagnosed with (exacerbation of) a chronic disease that can account for the onset of the PCC-like symptoms.
2. Being hospitalized or institutionalized at screening. Patients can be rescreened after discharge.
3. Presence of a serious medical condition that would prevent completion of follow-up.

4. Currently enrolled, or having been enrolled within the last 30 days, in any other study where that study's interventions or procedures may affect RECLAIM outcomes or procedures. Individuals can be rescreened after at least 30 days have passed since participation in such a study has been completed.

   The following exclusion criteria will apply to all potential participants WITHIN ONE TRIAL DOMAIN (these patients may still qualify for another trial domain):

5. The participant cannot be randomized to at least one IP arm and its control arm within a trial domain due to:

   1. Known hypersensitivity to an active IP ingredient or IP/placebo excipient;
   2. Receiving a treatment that is contraindicated to a trial IP;
   3. Already using a trial IP, or a drug in the same drug class as a trial IP, outside of the trial;
   4. Any other reason why a trial IP cannot be used, such as (risk of) pregnancy or breastfeeding or renal insufficiency.

During screening, these criteria will be assessed by licensed trial physicians. They will question the patient and verify prescription drug and contraceptive use, and other medical exclusion criteria, in each individual patient's medical and/or pharmacy records. The absence of pregnancy in women of childbearing potential has to be confirmed by a negative urine or serum pregnancy test.

Additional IP-specific in- and exclusion criteria, if any, are listed in relevant treatment-specific appendices to the core protocol. These also describe the latest information about drug interactions and contraindications as per the IP's SmPC/PIL.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

3

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Metformin	Drug: Metformin; Participants receive metformin tablets for a period of 12-weeks.
Experimental: Colchicine	Drug: colchicine; Participants receive colchicine tablets for a period of 12-weeks.
No Intervention: Usual care; Participants receive their standard of care for PCC, without starting any new medications during study participation.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Physical health-related quality of life (HRQoL)	PROMIS-29 physical health summary score	12 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Mental HRQoL	PROMIS-29 mental health summary score	12 weeks
Other aspects of HRQoL	PROMIS-29 domain scores: physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, sleep disturbance.	12 weeks
Fatigue	Checklist Individual Strength, fatigue severity subscale (CIS-8)	12 weeks
Post Exertional Malaise (PEM)	DePaul Symptom Questionnaire (DSQ-2) PEM questions	12 weeks
Cognitive functioning	PROMIS cognitive function 8a	12 weeks
Post Orthostatic Tachycardia Syndrome (POTS)	DSQ-2 POTS questions	12 weeks
Safety of IPs	Frequency of related and unrelated (S)AEs and SUSARs in each IP arm including their severity and outcome.	12 weeks
Tolerability of IPs	Level of adherence to each IP. Percent of participants with adequate adherence for the specific IP.	12 weeks
Durability of IP treatment responses	The proportion of participants that maintain HRQoL treatment success at 24 weeks.	24 weeks

Collaborators and Investigators

• Sponsor: Janneke van de Wijgert
• Collaborators: European Clinical Research Alliance for Infectious Diseases (ECRAID)

Study record dates

Study Major Dates

• Study Start (Actual): February 17, 2025
• Primary Completion (Estimated): December 1, 2027
• Study Completion (Estimated): December 1, 2027

Study Registration Dates

• First Submitted: December 1, 2025
• First Submitted That Met QC Criteria: December 1, 2025
• First Posted (Actual): December 12, 2025

Study Record Updates

• Last Update Posted (Actual): December 12, 2025
• Last Update Submitted That Met QC Criteria: December 1, 2025
• Last Verified: December 1, 2025

More Information

Terms related to this study

• Keywords: Metformin; Clinical trial; Intervention; Colchicine; Repurposed drugs; Post COVID condition; PAIS; Post Acute Sequelae of COVID-19
• Additional Relevant MeSH Terms: Post-Infectious Disorders; COVID-19; Pathologic Processes; Chronic Disease; Disease Attributes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; Pathological Conditions, Signs and Symptoms; Post-Acute COVID-19 Syndrome; Organic Chemicals; Heterocyclic Compounds; Alkaloids; Biguanides; Guanidines; Amidines; Metformin; Colchicine
• Other Study ID Numbers: EUCT 2024-511580-28; D-25-500086 (Other Identifier: NedMec Medical Research Ethics Committee, Utrecht, Netherlands)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No