Prednisolone and Vitamin B1/6/12 in Patients With Post-Covid-Syndrome (PreVitaCOV)

Wuerzburg University Hospital

Status and phase: Completed; Phase 3

Conditions: Post-COVID-19 Syndrome

Treatments: Drug: Prednisolone 20 mg/ 5 mg; Drug: Vitamin B compound (100mg B1, 50 mg B6, 500 µg B12); Drug: Placebo for Prednisolon; Drug: Placebo for Vitamin B compound

Study type: Interventional

Funder types: Other

Identifiers

NCT05638633

F001AM02222_1

2022-001041-20 (EudraCT Number)

Details and patient eligibility

About

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.

Full description

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

1. prove the feasibility of recruitment and retention of patients with PC19S in a primary care setting (pilot study, n=100)
2. 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.

Enrollment: 321 patients

Sex: All

Ages: 18+ years old

Volunteers: No Healthy Volunteers

Inclusion criteria

1. adult patients (at least 18 years old)
2. 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)
3. symptoms concerning at least one of the following domains: fatigue, dyspnea, cognition, anxiety, depression
4. 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

Exclusion criteria

1. acute Coronavirus disease (COVID-19) at baseline visit

2. patients who were treated in the intensive care unit because of COVID-19

3. pregnancy/ breastfeeding

4. diabetes mellitus

5. PC19S symptoms that can be explained by an alternative diagnosis

6. 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

7. 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.

8. 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

9. known allergies and contraindications to the intervention drugs

10. need of care and/or peer dependency

11. nursing home residents

12. inability to understand the scope of the study, to follow study procedures and to give informed consent or to attend the study sites

13. participation in another interventional trial at the same time or within the past 3 months before enrolment

14. 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)

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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321 participants in 4 patient groups, including a placebo group

1st arm (prednisolone and placebo)

Active Comparator group

Description:

Day 1-5: prednisolone 20mg 1x1 and placebo 1x1 Day 6-28: prednisolone 5mg 1x1 and placebo 1x1

Treatment:

Drug: Placebo for Vitamin B compound

Drug: Prednisolone 20 mg/ 5 mg

2nd arm (placebo and Vitamin B compound)

Active Comparator group

Description:

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

Treatment:

Drug: Placebo for Prednisolon

Drug: Vitamin B compound (100mg B1, 50 mg B6, 500 µg B12)

3rd arm (prednisolone and Vitamin B compound)

Active Comparator group

Description:

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

Treatment:

Drug: Vitamin B compound (100mg B1, 50 mg B6, 500 µg B12)

Drug: Prednisolone 20 mg/ 5 mg

4rd arm (placebo and placebo)

Placebo Comparator group

Description:

Day 1-5: Placebo 1x1 and placebo 1x1 Day 6-28: placebo 1x1 and placebo 1x1

Treatment:

Drug: Placebo for Vitamin B compound

Drug: Placebo for Prednisolon