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

NCT ID: NCT05638633

Last Updated: 2025-04-01

Basic Information

• Recruitment Status: COMPLETED
• Clinical Phase: PHASE3
• Total Enrollment: 321 participants
• Study Classification: INTERVENTIONAL
• Study Start Date: 2022-11-11
• Study Completion Date: 2025-01-30

Brief Summary

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.

Detailed 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.

Conditions

Post-COVID-19 Syndrome

Study Design

• Allocation Method: RANDOMIZED
• Intervention Model: PARALLEL
• Primary Study Purpose: TREATMENT
• Blinding Strategy: QUADRUPLE

Study Groups

1st arm (prednisolone and placebo)

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

Group Type: ACTIVE_COMPARATOR

Prednisolone 20 mg/ 5 mg

Intervention Type: DRUG

Administration of prednisolone 20 mg for 5 days, followed by prednisolone 5 mg for 23 days.

Placebo for Vitamin B compound

Intervention Type: DRUG

Administration of placebo for vitamin B compound placebo for 28 days.

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

Group Type: ACTIVE_COMPARATOR

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

Intervention Type: DRUG

Administration of vitamin B compound for 28 days.

Placebo for Prednisolon

Intervention Type: DRUG

Administration of placebo for prednisolone 20 mg for 5 days, followed by placebo for prednisolone 5 mg for 23 days.

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

Group Type: ACTIVE_COMPARATOR

Prednisolone 20 mg/ 5 mg

Intervention Type: DRUG

Administration of prednisolone 20 mg for 5 days, followed by prednisolone 5 mg for 23 days.

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

Intervention Type: DRUG

Administration of vitamin B compound for 28 days.

4rd arm (placebo and placebo)

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

Group Type: PLACEBO_COMPARATOR

Placebo for Vitamin B compound

Intervention Type: DRUG

Administration of placebo for vitamin B compound placebo for 28 days.

Placebo for Prednisolon

Intervention Type: DRUG

Administration of placebo for prednisolone 20 mg for 5 days, followed by placebo for prednisolone 5 mg for 23 days.

Interventions

Prednisolone 20 mg/ 5 mg

Administration of prednisolone 20 mg for 5 days, followed by prednisolone 5 mg for 23 days.

Intervention Type: DRUG

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

Administration of vitamin B compound for 28 days.

Intervention Type: DRUG

Placebo for Vitamin B compound

Administration of placebo for vitamin B compound placebo for 28 days.

Intervention Type: DRUG

Placebo for Prednisolon

Administration of placebo for prednisolone 20 mg for 5 days, followed by placebo for prednisolone 5 mg for 23 days.

Intervention Type: DRUG

Other Intervention Names

N.I.; Vitamin B complex forte; N.I.; N.I.

Eligibility Criteria

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)

• Minimum Eligible Age: 18 Years
• Eligible Sex: ALL
• Accepts Healthy Volunteers: No

Sponsors

University Hospital Tuebingen

OTHER

Sponsor Role: collaborator

University Hospital Schleswig-Holstein

OTHER

Sponsor Role: collaborator

Wuerzburg University Hospital

OTHER

Sponsor Role: lead

Responsible Party

Responsibility Role: SPONSOR

Principal Investigators

Ildikó Gágyor, Prof. Dr.

Role: STUDY_DIRECTOR

Director of Institute for General Practice Würzburg University Hospital

Locations

University Hospital Wuerzburg

Würzburg, Bavaria, Germany

Unversity Hospital Schleswig-Holstein

Kiel, , Germany

University Hospital Tuebingen

Tübingen, , Germany

Countries

Germany

Other Identifiers

2022-001041-20

Identifier Type: EUDRACT_NUMBER

Identifier Source: secondary_id

F001AM02222_1

Identifier Type: -

Identifier Source: org_study_id