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

Phase 3

Completed

• Conditions: Post-COVID-19 Syndrome
• Interventions: Drug: Vitamin B compound (100mg B1, 50 mg B6, 500 µg B12); Drug: Prednisolone 20 mg/ 5 mg; Drug: Placebo for Vitamin B compound; Drug: Placebo for Prednisolon

• Registration Number: NCT05638633
• Lead Sponsor: Wuerzburg University Hospital

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.

Study Timeline

• Study Start: 2022-11-11
• Study First Submitted: 2022-11-18
• Study First Submitted QC: 2022-12-01
• Study First Posted: 2022-12-06
• Primary Completion: 2025-01-30
• Study Completion: 2025-01-30
• Status Verified: 2025-03
• Last Update Submitted: 2025-03-31
• Last Update Posted: 2025-04-01

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 321

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)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
1st arm (prednisolone and placebo)	Placebo for Vitamin B compound	Day 1-5: prednisolone 20mg 1x1 and placebo 1x1 Day 6-28: prednisolone 5mg 1x1 and placebo 1x1
2nd arm (placebo and Vitamin B compound)	Vitamin B compound (100mg B1, 50 mg B6, 500 µg B12)	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
2nd arm (placebo and Vitamin B compound)	Placebo for Prednisolon	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
3rd arm (prednisolone and Vitamin B compound)	Vitamin B compound (100mg B1, 50 mg B6, 500 µg B12)	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
4rd arm (placebo and placebo)	Placebo for Vitamin B compound	Day 1-5: Placebo 1x1 and placebo 1x1 Day 6-28: placebo 1x1 and placebo 1x1
4rd arm (placebo and placebo)	Placebo for Prednisolon	Day 1-5: Placebo 1x1 and placebo 1x1 Day 6-28: placebo 1x1 and placebo 1x1
1st arm (prednisolone and placebo)	Prednisolone 20 mg/ 5 mg	Day 1-5: prednisolone 20mg 1x1 and placebo 1x1 Day 6-28: prednisolone 5mg 1x1 and placebo 1x1
3rd arm (prednisolone and Vitamin B compound)	Prednisolone 20 mg/ 5 mg	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

Primary Outcome Measures

Name	Time	Method
Confirmatory phase: Mean difference in PROMIS Total Score from day 0 to day 28	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	4 weeks	feasibility and acceptance of screening and recruitment in primary care; aim \> 85 % retention rate of 100 patients enrolled

Secondary Outcome Measures

Name	Time	Method
Overall assessment of functional status	6 months	Severity of PC19 symptom burden
visual analogue scale	6 months	Health related quality of life, 0 to 100 points, higher scores indicate a better outcome
Chalder Scale	6 months	Fatigue, 4 point rating scale, 0 to 33 points possible, higher values indicate a worse outcome
qualitative assessment of acceptance	6 months	qualitative interviews with subgroup sample
PC19 symptom list	6 months	checklist, number of subjectively present symptoms
PHQ 8	6 months	Depression, 4 point rating scale, 0 to 24 points possible, higher scores indicate a worse outcome
Numeric rating scale for pain	6 months	Pain, 10 point rating scale, higher values indicate a worse outcome
Testbatterie zur Aufmerksamkeitsprüfung (TAP)	4 weeks	cognitive function (Alertness: reaction time, distractibility: omissions and reaction time, divided attention: omissions, visual scanning: omissions and reaction time, flexibility: reaction time and errors)
PROMIS total and subscores	6 months	Severity of each PC19 symptom domain (patient reported outcome measurement information system (PROMIS))
feasibility/acceptance	6 months	exploratory questionnaire, rating scales and grades
Measure Yourself Medical Outcome Profile (MYMOP)	6 months	Severity of three subjectively chosen PC19 symptoms
EQ-5D-5L	6 months	Health related quality of life, 5 point rating scale, 0 to 20 points, higher scores indicate worse outcomes
Use of on-demand medication and change in concomitant medication	6 months	intake of on-demand medication, daily drug doses
Physical exercise	6 months	1minute Sit-to-Stand-Test, number of repetitions, BORG Scale, oxygen-saturation

Trial Locations

Locations (3)

Unversity Hospital Schleswig-Holstein; 🇩🇪 Kiel, Germany

University Hospital Wuerzburg; 🇩🇪 Würzburg, Bavaria, Germany

University Hospital Tuebingen; 🇩🇪 Tuebingen, Germany