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

Prednisolone and Vitamin B1, B6, and B12 in Patients With Post-COVID-19-Syndrome (PC19S) - a Randomized Controlled Trial in Primary Care

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.

Study Overview

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

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 Type: Interventional
• Enrollment (Actual): 321
• Phase: Phase 3

Contacts and Locations

Study Locations

• Germany
  • Kiel, Germany
    • Unversity Hospital Schleswig-Holstein
  • Tuebingen, Germany
    • University Hospital Tuebingen
  • Bavaria
    • Würzburg, Bavaria, Germany, 97080
      • University Hospital Wuerzburg

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No

Description

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 Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: 1st arm (prednisolone and placebo); Day 1-5: prednisolone 20mg 1x1 and placebo 1x1 Day 6-28: prednisolone 5mg 1x1 and placebo 1x1	Drug: Prednisolone 20 mg/ 5 mg; Administration of prednisolone 20 mg for 5 days, followed by prednisolone 5 mg for 23 days.; Other Names: N.I.; Drug: Placebo for Vitamin B compound; Administration of placebo for vitamin B compound placebo for 28 days.; Other Names: N.I.
Active Comparator: 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	Drug: Vitamin B compound (100mg B1, 50 mg B6, 500 µg B12); Administration of vitamin B compound for 28 days.; Other Names: Vitamin B complex forte; Drug: Placebo for Prednisolon; Administration of placebo for prednisolone 20 mg for 5 days, followed by placebo for prednisolone 5 mg for 23 days.; Other Names: N.I.
Active Comparator: 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	Drug: Prednisolone 20 mg/ 5 mg; Administration of prednisolone 20 mg for 5 days, followed by prednisolone 5 mg for 23 days.; Other Names: N.I.; Drug: Vitamin B compound (100mg B1, 50 mg B6, 500 µg B12); Administration of vitamin B compound for 28 days.; Other Names: Vitamin B complex forte
Placebo Comparator: 4rd arm (placebo and placebo); Day 1-5: Placebo 1x1 and placebo 1x1 Day 6-28: placebo 1x1 and placebo 1x1	Drug: Placebo for Vitamin B compound; Administration of placebo for vitamin B compound placebo for 28 days.; Other Names: N.I.; Drug: Placebo for Prednisolon; Administration of placebo for prednisolone 20 mg for 5 days, followed by placebo for prednisolone 5 mg for 23 days.; Other Names: N.I.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pilot phase: Proportion of participants retained after 28 days	feasibility and acceptance of screening and recruitment in primary care; aim > 85 % retention rate of 100 patients enrolled	4 weeks
Confirmatory phase: Mean difference in PROMIS Total Score from day 0 to day 28	change in symptom severity to day 28 as assessed by specifically tailored total score based on the patient reported outcome measurement information system (PROMIS)	4 weeks

Secondary Outcome Measures

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

Collaborators and Investigators

• Sponsor: Wuerzburg University Hospital
• Collaborators: University Hospital Tuebingen; University Hospital Schleswig-Holstein
• Investigators: Study Director: Ildikó Gágyor, Prof. Dr., Director of Institute for General Practice Würzburg University Hospital

Study record dates

Study Major Dates

• Study Start (Actual): November 11, 2022
• Primary Completion (Actual): January 30, 2025
• Study Completion (Actual): January 30, 2025

Study Registration Dates

• First Submitted: November 18, 2022
• First Submitted That Met QC Criteria: December 1, 2022
• First Posted (Actual): December 6, 2022

Study Record Updates

• Last Update Posted (Actual): April 1, 2025
• Last Update Submitted That Met QC Criteria: March 31, 2025
• Last Verified: March 1, 2025

More Information

Terms related to this study

• Keywords: Fatigue; Vitamin B12; Prednisolone; Vitamin B1; Vitamin B6; PC19S; ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome)
• Additional Relevant MeSH Terms: Pathologic Processes; Respiratory Tract Infections; Infections; RNA Virus Infections; Virus Diseases; Respiratory Tract Diseases; Disease; Lung Diseases; Pneumonia, Viral; Pneumonia; Coronavirus Infections; Coronaviridae Infections; Nidovirales Infections; COVID-19; Syndrome; Antineoplastic Agents; Physiological Effects of Drugs; Anti-Inflammatory Agents; Antiemetics; Autonomic Agents; Peripheral Nervous System Agents; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Micronutrients; Protective Agents; Neuroprotective Agents; Methylprednisolone Acetate; Prednisolone; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate; Vitamins; Vitamin B Complex; Corticosterone
• Other Study ID Numbers: F001AM02222_1; 2022-001041-20 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No