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.\tPositive SARS-CoV-2 nucleic acid amplification test (NAAT), such as PCR; b.\tPositive SARS-CoV-2 rapid diagnostic test, including home-administered tests; c.\tCOVID-19 diagnosis by a medical specialist (GP or in-hospital), based on the above or other clinical tests and assessments.\n- Willing and able to provide informed consent via e-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- Applicable to all potential participants within one trial domain: 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.\tKnown hypersensitivity to an active IP ingredient or excipient; b.\tReceiving a treatment that is contraindicated to a trial IP; c.\tAlready using a trial IP, or a drug in the same drug class as a trial IP, outside of the trial; d.\tAny other reason why a trial IP cannot be used, such as (risk of) pregnancy or breastfeeding. During screening, these criteria will be assessed by questioning the patient, verification of prescription drug and contraceptive use in medical and/or pharmacy records, and verification of other exclusion criteria if indicated in the TSA. The absence of pregnancy in women of childbearing potential will be confirmed by a negative urine or serum pregnancy test. Refer to section 8.2.1. for more details about pregnancy exclusion at inclusion and pregnancy prevention during follow-up."}

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":"Assessed at 12 weeks using the PROMIS-29 instrument; primary measure is the PROMIS-29 physical health summary score (assessment at end of trial 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":"Assessed at 12 weeks using PROMIS-29 mental health summary score and individual PROMIS-29 domain scores (physical function, fatigue, pain interference, depressive symptoms, anxiety, social participation, sleep disturbance)."}
• {"endpoint_text":"- Assessed at 12 weeks: ●\tChecklist Individual Strength (CIS-20R) ●\tDePaul Symptom Questionnaire (DSQ-2) PEM questions ●\tPROMIS cognitive function 8a ●\tDSQ-2 POTS questions","definition_or_measurement_approach":"Assessed at 12 weeks using CIS-20R, DSQ-2 PEM items, PROMIS cognitive function 8a, and DSQ-2 POTS items."}
• {"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":"Assessed at 12 weeks by recording frequency, severity and outcomes of related and unrelated adverse events and serious adverse events in each IP arm versus 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":"Assessed at 12 weeks by measuring adherence levels for each IP compared with matching placebo control (if available) and calculating percentage of participants meeting predefined adequate adherence thresholds."}
• {"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) by determining proportion of participants who maintain the HRQoL treatment success defined at 12 weeks."}
• {"endpoint_text":"- Exploratory: Same as above but stratified by phenotype.","definition_or_measurement_approach":"Exploratory analyses stratifying the above endpoints by PASC phenotype as defined in trial-specific analysis plans/TSAs."}
• {"endpoint_text":"- Exploratory: Same as above but stratified by pre-enrolment PASC symptom(s) duration.","definition_or_measurement_approach":"Exploratory analyses stratifying the above endpoints 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 Trial Specific Appendices (TSAs); specific measures not provided in the available summary."}
• {"endpoint_text":"- Exploratory: Described in relevant TSAs.","definition_or_measurement_approach":"Exploratory endpoints and analyses as described in the relevant TSAs; detailed definitions available in those documents."}

Other endpoints

• {"endpoint_text":"- Exploratory: Same as above but stratified by phenotype.","definition_or_measurement_approach":"Exploratory: analyses of primary/secondary endpoints stratified by PASC phenotype (details in TSAs)."}
• {"endpoint_text":"- Exploratory: Same as above but stratified by pre-enrolment PASC symptom(s) duration.","definition_or_measurement_approach":"Exploratory: analyses stratified by pre-enrolment PASC symptom duration (details in TSAs)."}
• {"endpoint_text":"- Exploratory: Described in relevant TSAs.","definition_or_measurement_approach":"Exploratory endpoints described in relevant Trial Specific Appendices (TSAs); specifics not provided in available data."}
• {"endpoint_text":"- Exploratory: Described in relevant TSAs.","definition_or_measurement_approach":"Exploratory endpoints described in relevant TSAs; specifics not provided in available data."}

Netherlands

Earliest CTIS Part Ii Submission Date

08-05-2024

Latest Decision Or Authorization Date

22-08-2024

Processing Time Days

106

Number Of Sites

1

Number Of Participants

1500

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":"Stichting Long Covid","duties_or_roles":"Monetary support","organisation_type":""}
• {"country":"","full_name":"ZonMW","duties_or_roles":"Monetary support","organisation_type":""}