METFORMIN for Post-acute sequelae of SARS-CoV-2 infection (PASC)

Inclusion criteria

• {"criterion_text":"- Adults aged 18 years or older.\n- Residing in the study area (defined in each respective CSA) for the duration of trial participation.\n- Persistent PASC signs and 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.\n- Self-reported confirmation of having had a SARS-CoV-2 infection by: a. Positive SARS-CoV-2 nucleic acid amplification test (NAAT), such as PCR; b. Positive SARS-CoV-2 rapid diagnostic test, including home-administered tests; c. COVID-19 diagnosis by a treating physician (GP or medical specialist), based on the above or other clinical tests and assessments. Alternatively, a treating physician may have diagnosed the patient with PASC, thereby implicitly acknowledging that the patient had COVID-19 in the past.\n- Willing and able to provide informed consent\n- Willing and able to perform trial procedures\n- Allowing their GP/pharmacy and the RECLAIM trial team to exchange medical information that is relevant for the participant’s safety and trial assessments."}

Exclusion criteria

• {"criterion_text":"- Having been diagnosed with (exacerbation of) a chronic disease that can account for the onset of the PASC-like symptoms.\n- Being hospitalised or institutionalised at screening. Patients can be rescreened after discharge.\n- Presence of a serious medical condition that would prevent completion of follow-up.\n- 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.\n- Having initiated chronic use of a new licensed medication for any indication in the three months prior to the eligibility confirmation by a trial physician. This criterion may be reassessed after sufficient time has passed. Similarly, the potential participant should commit to not starting any chronic use of new licensed medications for any indication between eligibility confirmation and Week-12 unless medically necessary as determined by a treating physician (see section 8.1.1.1).\n- The following exclusion criteria will apply to all potential participants WITHIN ONE TRIAL DOMAIN (these patients may still qualify for another trial domain): 6 The participant cannot be randomised to at least one IP arm and its control arm within a trial domain due to (refer to relevant TSAs for details): a. Known hypersensitivity to an active IP ingredient or IP/placebo excipient; b. Receiving a treatment that is contraindicated to a trial IP; c. Already using a trial IP, or a drug in the same drug class as a trial IP, outside of the trial; d. Any other reason why a trial IP cannot be used, such as (risk of) pregnancy or breastfeeding or renal insufficiency."}

Primary endpoints

• {"endpoint_text":"- Assessed at 12 weeks (end of trial product use period): Patient-Reported Outcomes Measurement Information System Profile29 (PROMIS-29) physical health summary score","definition_or_measurement_approach":"Measured at 12 weeks using the PROMIS-29 instrument; primary measure is the PROMIS-29 physical health summary score assessed at 12 weeks (end of product use period)."}

Secondary endpoints

• {"endpoint_text":"- Assessed at 12 weeks: ●\tPROMIS-29 mental health summary score ●\tPROMIS-29 domain scores: physical function, fatigue, pain interference, depressive symptoms, anxiety, ability to participate in social roles and activities, sleep disturbance.","definition_or_measurement_approach":"Measured at 12 weeks using PROMIS-29 mental health summary score and individual PROMIS-29 domain scores."}
• {"endpoint_text":"- Assessed at 12 weeks: ●\tChecklist Individual Strength (CIS-8) ●\tDePaul Symptom Questionnaire (DSQ-2) PEM questions ●\tPROMIS cognitive function 8a ●\tDSQ-2 POTS questions","definition_or_measurement_approach":"Measured at 12 weeks using CIS-8, DSQ-2 PEM items, PROMIS cognitive function 8a, and DSQ-2 POTS questions."}
• {"endpoint_text":"- Assessed at 12 weeks: ●\tFrequency of related and unrelated (S)AEs in each IP arm compared to its control arm including their severity and outcome.","definition_or_measurement_approach":"Safety assessment at 12 weeks comparing frequency, severity and outcomes of (S)AEs between each IP arm and its control arm."}
• {"endpoint_text":"- Assessed at 12 weeks: ●\tLevel of adherence to each IP versus the matching placebo control (if available). ●\tPercent of participants with adequate adherence for the specific IP.","definition_or_measurement_approach":"Adherence levels assessed at 12 weeks; percent of participants meeting criteria for adequate adherence reported per IP versus matching placebo."}
• {"endpoint_text":"- Assessed at 24 weeks (12 weeks after cessation of IP use): The proportion of participants that maintain HRQoL treatment success at 12 weeks.","definition_or_measurement_approach":"Assessed at 24 weeks (12 weeks post-IP cessation): proportion maintaining HRQoL treatment success measured at 12 weeks."}
• {"endpoint_text":"- Exploratory: Same as above but stratified by phenotype.","definition_or_measurement_approach":"Exploratory analyses stratified by PASC phenotype as defined in trial-specific analysis (TSAs)."}
• {"endpoint_text":"- Exploratory: Same as above but stratified by pre-enrolment PASC symptom(s) duration.","definition_or_measurement_approach":"Exploratory analyses stratified by duration of PASC symptoms prior to enrolment."}
• {"endpoint_text":"- Exploratory: Described in relevant TSAs.","definition_or_measurement_approach":"Exploratory endpoints and analyses as described in the relevant Treatment Specific Appendices (TSAs)."}
• {"endpoint_text":"- Exploratory: Described in relevant TSAs.","definition_or_measurement_approach":"Exploratory endpoints and analyses as described in the relevant TSAs."}

Other endpoints

• {"endpoint_text":"- Exploratory: Same as above but stratified by phenotype.\n- Exploratory: Same as above but stratified by pre-enrolment PASC symptom(s) duration.\n- Exploratory: Described in relevant TSAs.\n- Exploratory: Described in relevant TSAs.","definition_or_measurement_approach":"Exploratory endpoints include phenotype- and symptom-duration-stratified analyses and additional exploratory analyses defined in Treatment Specific Appendices (TSAs); measurement approaches follow the same instruments (PROMIS-29, CIS-8, DSQ-2, PROMIS cognitive measures, safety assessments) as specified for primary/secondary endpoints."}

Methods

• Study website (RECLAIM Website) — digital outreach to potential participants with PASC (document: K2_Recruitment material_RECLAIM Website_Clean).
• Printed materials: Flyer and Poster (documents: K2_Recruitment material_Flyer_Clean; K2_Recruitment material_Poster_Clean) targeted at persons with PASC and local outreach in study area(s).
• Local site recruitment (residence in study area required as per inclusion criterion) through participating site(s) in the Netherlands.

Netherlands

Earliest CTIS Part Ii Submission Date

29-01-2025

Latest Decision Or Authorization Date

04-09-2025

Processing Time Days

218

Number Of Sites

1

Number Of Participants

2000

Primary sponsor

Full Name

Universitair Medisch Centrum Utrecht

Organisation Type

Hospital/Clinic/Other health care facility

Country Of Registered Address

Netherlands

Third parties

• {"country":"","full_name":"ZonMW","duties_or_roles":"Source of monetary support / funder","organisation_type":""}
• {"country":"","full_name":"Stichting Long Covid","duties_or_roles":"Source of monetary support / funder","organisation_type":""}