A trial evaluating treatments for Long COVID-19 symptoms

An Adaptive, Randomized, doublE-blind, Placebo-controlled, Prospective, Pharmacological interVention Study In Participants With Long COVID-19 Syndrome: REVIVE-TOGETHER Trial

This study is testing whether the medications Fluvoxamine and Metformin can help adults with Long COVID-19 symptoms feel better.

Quick facts

• Phase: Phase 3
• Study type: Interventional
• Enrollment: 1500 (estimated)
• Ages: 18 Years and up
• Sex: All
• Sponsor: Cardresearch (Academic / other)
• Locations: 6 sites (Belo Horizonte, Minas Gerais and 5 other locations)
• Trial ID: NCT06128967 on ClinicalTrials.gov

What this trial studies

This multicenter, adaptive, randomized, double-blinded, placebo-controlled trial aims to assess the efficacy of Fluvoxamine and Metformin in treating persistent symptoms associated with Long COVID-19. Participants will be individuals aged 18 and older who have experienced a confirmed case of COVID-19 and exhibit symptoms consistent with Long COVID. The study will focus on chronic immune-inflammatory modulation to alleviate debilitating symptoms that can last for months or years. The trial is designed to gather robust data to inform future treatment options for this condition.

Who should consider this trial

Good fit: Ideal candidates are adults aged 18 and older with a confirmed history of COVID-19 and persistent fatigue symptoms.

Not a fit: Patients who are currently hospitalized or have severe acute symptoms may not benefit from this study.

Why it matters

Potential benefit: If successful, this trial could lead to effective therapies for managing Long COVID-19 symptoms, improving patients' quality of life.

How similar studies have performed: While several small-scale pilot studies have been conducted, this adaptive trial represents a novel and larger-scale approach to addressing Long COVID-19.

Eligibility criteria

Inclusion Criteria:

1. Age 18 years or older at the time of screening.
2. Willing and able to provide written informed consent, or with a legal representative who can provide informed consent (where approved locally and nationally).
3. Previous confirmed case of SARS-CoV-2 infection (e.g., reports having a positive nucleic acid amplification test or a professional-use SARS-CoV-2 rapid antigen diagnostic test or positive self-test).
4. Participants with a clinical picture compatible with LONG COVID according to international definitions: (www.nice.org.uk/guidance/ng188, https://www.who.int/publications/i/item/WHO-2019-nCoV-Post_COVID -19_condition-Clinical_case_definition-2021.1), and fatigue symptoms with an average score of at least 03 on the Fatigue Analog Scale (FSS)
5. Not currently hospitalized or requiring hospitalization, or having been hospitalized in an intensive care center at the time of the COVID-19 episode.
6. Participants with the following vital data:

   1. Heart Rate between 55 and 100 bpm;
   2. Temperature below 38o C;
   3. Oxygen saturation ≥ 95%.
7. Patients of childbearing potential or with partners of childbearing potential must agree to use adequate contraception during the study and up to 90 days of follow-up.
8. The symptoms of fatigue cannot be attributed to any other cause (in the researcher's opinion).
9. Willingness to follow all study procedures.

Exclusion Criteria:

1. Known acute SARS-CoV-2 infection;
2. Inability to understand the content of the Informed Consent Form or to follow the study procedures;
3. Known previous diagnosis of malignant encephalomyelitis/chronic fatigue syndrome, unrelated to SARS-CoV-2 infection;
4. Known pre-existing dysautonomia, unrelated to SARS-CoV-2 infection;
5. Diabetes mellitus (exclusion criteria for the Metformin and Metformin Placebo arm);
6. Known stroke within 3 months prior to screening;
7. Known severe anemia, defined as \< 8 g/dl;
8. Body Mass Index (BMI) \> 35.
9. Known diagnosis of Lyme disease;
10. Any use of illicit drugs not related to marijuana within 30 days prior to informed consent;
11. Pregnant women or women of childbearing age who do not agree to practice an effective method of contraception within 90 days from the date of signing this consent form;
12. Breastfeeding women;
13. Participants using serotonin reuptake inhibitors (donepezil, fluoxetine, escitalopran, parorexitin);
14. Participants chronically using any of the medications under evaluation (metformin and fluvoxamine);
15. Severe current comorbid psychiatric disorder (e.g., clinical depression, anxiety, sleep disorder, eating disorder, substance abuse), uncontrolled and associated with significant symptoms or requiring the use of a medication contraindicated in this research ;
16. Clinical history of moderate to severe hepatic impairment or liver cirrhosis with Child-Pugh classification C or greater;
17. Clinical history of severe lung disease with significant limitation of activities;
18. Inability of the participant to give consent or adhere to the procedures proposed in the study;
19. Taking medications which are known to cause a known side effect of chronic fatigue;
20. Known hypersensitivity and/or intolerance to Fluvoxamine or Metformin;
21. Any clinical condition which, in the investigator's opinion, may prevent participation in this research.

Where this trial is running

Belo Horizonte, Minas Gerais and 5 other locations

• CARDRESEARCH - Cardiologia Assistencial e de Pesquisa — Belo Horizonte, Minas Gerais, Brazil (Recruiting)
• City of Brumadinho — Brumadinho, Minas Gerais, Brazil (Not_yet_recruiting)
• Governador Valadares City Public Health Authority — Governador Valadares, Minas Gerais, Brazil (Recruiting)
• City of Ibirité Public Health Authority — Ibirité, Minas Gerais, Brazil (Recruiting)
• Sociedade Padrao de Educacao Superior — Montes Claros, Minas Gerais, Brazil (Not_yet_recruiting)
• Universidade Federal de Ouro Preto — Ouro Preto, Minas Gerais, Brazil (Not_yet_recruiting)

Study contacts

• Study coordinator: Gilmar Reis, MD, PhD

Conditions Long COVID-19 Syndrome; Chronic Fatigue Syndrome; Fluvoxamine; Metformin; Adaptive Trial Design; Randomized Controlled Trial