Prednisolone and Vitamin B1, B6, and B12 in Patients With Post-COVID-19-Syndrome (PC19S) - a Randomized Controlled Trial in Primary Care
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 321
- 试验地点
- 3
- 主要终点
- Confirmatory phase: Mean difference in PROMIS Total Score from day 0 to day 28
研究概览
简要总结
This is a multicenter, randomized, placebo controlled, double-blind phase III trial with four parallel groups studying studying the feasibility of RCT in primary care as well as the effectiveness of treatment with prednisolone and/or vitamin B1/6/12 for PC19S.
详细描述
PC19S affects a considerable portion of patients after an infection with SARS-CoV-2 with a broad range of disabling symptoms. Neurotropic vitamins such as vitamins B1, B6, an B12, and drugs with anti-inflammatory properties such as corticosteroids were suggested to alleviate symptoms. The trial is designed as a two-step approach that will
- prove the feasibility of recruitment and retention of patients with PC19S in a primary care setting (pilot study, n=100)
- investigate the effectiveness and safety of the treatment drugs alone and of their combination (confirmatory study, n= 340).
The pilot study will be transformed into a confirmatory study if feasibility is given, defined as retention rate of 85% after enrollment of 100 patients. Or on recommendation of the Data Safety and Monitoring Board (DSMB).
In addition, blood samples wil be analysed for routine parameters and vitamin B12 derivates as well as cytokines.
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
blinded labelling of the study drug by the Hospital pharmacy of the Charité
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
- •adult patients (at least 18 years old)
- •history of SARS-CoV-2 infection at least 12 weeks ago (the infection must be documented by either a positive PCR or antibody-Test or be confirmed by the patient's GP)
- •symptoms concerning at least one of the following domains: fatigue, dyspnea, cognition, anxiety, depression
- •above mentioned symptom(s) that developed during or after the SARS-CoV-2 infection, that persist until study inclusion, and that are associated with COVID 19 as assessed by the patients' general practitioner or the local investigator
排除标准
- •acute Coronavirus disease (COVID-19) at baseline visit
- •patients who were treated in the intensive care unit because of COVID-19
- •pregnancy/ breastfeeding
- •diabetes mellitus
- •PC19S symptoms that can be explained by an alternative diagnosis
- •History of severe medical conditions such as
- •concomitant acute infectious disease
- •gastrointestinal ulcer
- •liver disease/liver cirrhosis
- •malabsorption or condition after bariatric surgery
- •chronic airway disease
- •chronic heart failure [New York Heart Association (NYHA) III and IV]
- •neurological disorders
- •untreated hypothyroidism
- •significantly impaired glucuronidation
- •immunodeficiency or a chronically weakened immune system
- •mental disorders
- •active cancer
- •any other severe medical conditions that preclude participation as determined by responsible physician
- •current use of
- •immunosuppressive drugs
- •non-steroidal antiinflammatory drugs (NSAID)
- •fluoroquinolones
- •anticoagulation
- •any other drug that could exhibit clinically relevant interactions with the study medication (as described in Fachinformation Prednisolon STADA®, Predni H Tablinen® Zentiva or Fachinformation Vitamin B komplex Hevert). The decision on the clinical relevance of the interactions is at the discretion of the clinical investigator.
- •systemic treatment with prednisolone for at least 7 days or any parenteral application since the end of the acute phase of COVID-19; treatment with vitamins B1, B6, or B12 in doses equivalent to the dose of the study medi-cation for at least 7 days or any parenteral application since the end of the acute phase of COVID-19; vitamin supplements containing vitamin B1, B6, or B12 should have been ceased at least 4 weeks prior to the inclusion of the study
- •known allergies and contraindications to the intervention drugs
- •need of care and/or peer dependency
- •nursing home residents
- •inability to understand the scope of the study, to follow study procedures and to give informed consent or to attend the study sites
- •participation in another interventional trial at the same time or within the past 3 months before enrolment
- •female patients considering to get pregnant during the first month of the trial and within 1 week after the last dose of study drug(s)
研究组 & 干预措施
1st arm (prednisolone and placebo)
Day 1-5: prednisolone 20mg 1x1 and placebo 1x1 Day 6-28: prednisolone 5mg 1x1 and placebo 1x1
干预措施: Prednisolone 20 mg/ 5 mg (Drug)
1st arm (prednisolone and placebo)
Day 1-5: prednisolone 20mg 1x1 and placebo 1x1 Day 6-28: prednisolone 5mg 1x1 and placebo 1x1
干预措施: Placebo for Vitamin B compound (Drug)
2nd arm (placebo and Vitamin B compound)
Day 1-5: Placebo 1x1 and Vitamin B compound (100 mg B1, 50 mg B6, 500µ B12) 1x1 Day 6-28: placebo 1x1 and Vitamin B compound (100 mg B1, 50 mg B6, 500 µg B12) 1x1
干预措施: Vitamin B compound (100mg B1, 50 mg B6, 500 µg B12) (Drug)
2nd arm (placebo and Vitamin B compound)
Day 1-5: Placebo 1x1 and Vitamin B compound (100 mg B1, 50 mg B6, 500µ B12) 1x1 Day 6-28: placebo 1x1 and Vitamin B compound (100 mg B1, 50 mg B6, 500 µg B12) 1x1
干预措施: Placebo for Prednisolon (Drug)
3rd arm (prednisolone and Vitamin B compound)
Day 1-5: prednisolone 20mg 1x1 and Vitamin B compound (100 mg B1, 50 mg B6, 500µg B12) 1x1 Day 6-28: prednisolone 5mg 1x1 and Vitamin B compound (100 mg B1, 50mg B6, 500µg B12) 1x1
干预措施: Prednisolone 20 mg/ 5 mg (Drug)
3rd arm (prednisolone and Vitamin B compound)
Day 1-5: prednisolone 20mg 1x1 and Vitamin B compound (100 mg B1, 50 mg B6, 500µg B12) 1x1 Day 6-28: prednisolone 5mg 1x1 and Vitamin B compound (100 mg B1, 50mg B6, 500µg B12) 1x1
干预措施: Vitamin B compound (100mg B1, 50 mg B6, 500 µg B12) (Drug)
4rd arm (placebo and placebo)
Day 1-5: Placebo 1x1 and placebo 1x1 Day 6-28: placebo 1x1 and placebo 1x1
干预措施: Placebo for Vitamin B compound (Drug)
4rd arm (placebo and placebo)
Day 1-5: Placebo 1x1 and placebo 1x1 Day 6-28: placebo 1x1 and placebo 1x1
干预措施: Placebo for Prednisolon (Drug)
结局指标
主要结局
Confirmatory phase: Mean difference in PROMIS Total Score from day 0 to day 28
时间窗: 4 weeks
change in symptom severity to day 28 as assessed by specifically tailored total score based on the patient reported outcome measurement information system (PROMIS)
Pilot phase: Proportion of participants retained after 28 days
时间窗: 4 weeks
feasibility and acceptance of screening and recruitment in primary care; aim \> 85 % retention rate of 100 patients enrolled
次要结局
- Overall assessment of functional status(6 months)
- visual analogue scale(6 months)
- Chalder Scale(6 months)
- PC19 symptom list(6 months)
- PHQ 8(6 months)
- Numeric rating scale for pain(6 months)
- Testbatterie zur Aufmerksamkeitsprüfung (TAP)(4 weeks)
- PROMIS total and subscores(6 months)
- feasibility/acceptance(6 months)
- Measure Yourself Medical Outcome Profile (MYMOP)(6 months)
- qualitative assessment of acceptance(6 months)
- Use of on-demand medication and change in concomitant medication(6 months)
- EQ-5D-5L(6 months)
- Physical exercise(6 months)