An Adaptive, Randomized, doublE-blind, Placebo-controlled, Prospective, Pharmacological interVention Study In Participants With Long COVID-19 Syndrome: REVIVE-TOGETHER Trial
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 399
- 试验地点
- 11
- 主要终点
- Improvement on Fatigue Severity Score Scale (FSS)
研究概览
简要总结
IRB approval date 14-APR-2024 and public at https://plataformabrasil.saude.gov.br/login.jsf since IURB approval
Long COVID is a multi-systemic condition comprising often severe and persistent symptoms (longer than 12 weeks) that follow a known episode of COVID-19 and cannot be explained by another medical condition. This condition is observed in up to 15% of all individuals after an acute episode of COVID-19, even in those who had a mild and oligosymptomatic SARS-CoV-2 infection. Around 40% of these patients present symptoms that significantly compromise their daily activities.
There is increasing evidence that LONG COVID is accompanied by dysregulated, persistent and uncontrolled inflammation, often accompanied by the development of an autoreactive immune response, including autoantibodies. Symptoms can last months or years, particularly in cases of chronic fatigue syndrome, with significant proportions of individuals having significant chronic impairment, preventing the performance of work and social activities.
详细描述
There is currently no approved therapies for Long COVID. Several clinical trials have been developed to address this clinical condition, however the results were based on small-scale pilot studies. We developed this adaptive, large-scale, prospective, double-blind clinical trial to evaluate the effect of chronic immune-inflammatory modulation on persistent Long-COVID symptoms.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
The production of medication bottles is carried out by a pharmaceutical company, which does not have access to members of the research centers. The pills are similar in shape, color, size and weight and are packaged in identical bottles and coded according to each medication arm, this code being inaccessible to the investigator, the sponsor, the medical care provider and the research participant.
The allocation process follows a random sequential distribution into blocks. The posology of the medications is identical for all arms.
入排标准
- 年龄范围
- 18 Years 至 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Age 18 years or older at the time of screening.
- •Willing and able to provide written informed consent, or with a legal representative who can provide informed consent (where approved locally and nationally).
- •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).
- •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)
- •Last COVID-19 episode within 24 months of screening.
- •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:
- •Heart Rate between 55 and 100 bpm;
- •Temperature below 38o C;
- •Oxygen saturation ≥ 95%.
- •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.
排除标准
- •Known acute SARS-CoV-2 infection;
- •Inability to understand the content of the Informed Consent Form or to follow the study procedures;
- •Known previous diagnosis of malignant encephalomyelitis/chronic fatigue syndrome, unrelated to SARS-CoV-2 infection;
- •Known pre-existing dysautonomia, unrelated to SARS-CoV-2 infection;
- •Diabetes mellitus (exclusion criteria for the Metformin and Metformin Placebo arm);
- •Known Creatinin Clearance < 30 ml/ min or under chronic renal replacement therapy;
- •Known stroke within 3 months prior to screening;
- •Known severe anemia, defined as < 8 g/dl;
- •Body Mass Index (BMI) >
- •Known diagnosis of Lyme disease;
- •Any use of illicit drugs not related to marijuana within 30 days prior to informed consent;
- •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;
- •Breastfeeding women;
- •Expected hospitalization for elective surgical procedures that will ensure hospitalization > 48 hs;
- •Contra-indications for Metformin arm eligibility:
- •Participant currently on metformin use;
- •Participants with known creatinine clearance < 30 ml/min, history of KDIGO IV or under renal replacement therapy;
- •Contra-indications for Fluvoxamin arm eligibility:
- •a. Current use of serotonin reuptake inhibitors (donepezil, Fluoxetine, Escitalopran, Paroxetine
- •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 ;
- •Clinical history of moderate to severe hepatic impairment or liver cirrhosis with Child-Pugh classification C or greater;
- •Clinical history of severe lung disease with significant limitation of activities;
- •Inability of the participant to give consent or adhere to the procedures proposed in the study;
- •Taking medications which are known to cause a known side effect of chronic fatigue (except for participants with cardiovascular disease and chronic use of beta-blockers);
- •Known hypersensitivity and/or intolerance to Fluvoxamine or Metformin;
- •Any clinical condition which, in the investigator's opinion, may prevent participation in this research.
研究组 & 干预措施
Fluvoxamine 100 mg
Fluvoxamine maleate 100 mg pills dispensed in coded bottles. Each bottle contains 120 pills
干预措施: Placebo (Drug)
Metformin XR 500 mg
Metformin 500 mg Extended release pills dispensed in coded bottles. Each bottle contains 120 pills
干预措施: Placebo (Drug)
Placebo
Placebo talc pills of same shape, color, weight dispensed in coded bottles. Each bottle contains 120 pills
干预措施: Fluvoxamine Maleate 100 MG (Drug)
Placebo
Placebo talc pills of same shape, color, weight dispensed in coded bottles. Each bottle contains 120 pills
干预措施: Metformin Extended Release Oral Tablet (Drug)
结局指标
主要结局
Improvement on Fatigue Severity Score Scale (FSS)
时间窗: Day 60 after randomization
Improvement on Fatigue Severity Score Scale (FSS)
次要结局
- Reduction on any cause hospitalization(Day 60 after randomization)
- Safety of Fluvoxamine(Since randomization up to Day 60 (last IMP dose))
- Improvement on Fatigue Severity Score Scale (FSS)(Day 30 post Study Drug Termination (Day 90 after randomization))
- Safety of metformin(Since randomization up to Day 60 (last IMP dose))
- Death of any cause(Since randomization up to Day 60 (last IMP dose))
- Improvement on Fatigue Severity Score Scale (FSS)(Day 30 after randomization)