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

Sponsor

Wuerzburg University Hospital (Other)

Overall Status

Recruiting

CT.gov ID

NCT05638633

Collaborator

University Hospital Tuebingen (Other), University Hospital Schleswig-Holstein (Other)

340

Enrollment

Locations

Arms

19.6

Anticipated Duration (Months)

113.3

Patients Per Site

5.8

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Post-COVID-19 Syndrome	Drug: Prednisolone 20 mg/ 5 mg Drug: Vitamin B compound (100mg B1, 50 mg B6, 500 µg B12) Drug: Placebo for Vitamin B compound Drug: Placebo for Prednisolon	Phase 3

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

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.

Study Design

Study Type:

Interventional

Anticipated Enrollment :

340 participants

Allocation:

Randomized

Intervention Model:

Parallel Assignment

Intervention Model Description:

after Baseline, Randomization to 4 arms: st arm (prednisolone and placebo) nd arm (placebo an Vitamin B compound) rd arm (prednisolone and Vitamin B compound) th arm (placebo and placebo)after Baseline, Randomization to 4 arms: st arm (prednisolone and placebo) nd arm (placebo an Vitamin B compound) rd arm (prednisolone and Vitamin B compound) th arm (placebo and placebo)

Masking:

Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)

Masking Description:

blinded labelling of the study drug by the Hospital pharmacy of the Charité

Primary Purpose:

Treatment

Official Title:

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

Actual Study Start Date :

Nov 11, 2022

Anticipated Primary Completion Date :

Jun 30, 2024

Anticipated Study Completion Date :

Jun 30, 2024

Arms and Interventions

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.

Outcome Measures

Primary Outcome Measures

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
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)

Secondary Outcome Measures

PROMIS total and subscores [6 months]
Severity of each PC19 symptom domain (patient reported outcome measurement information system (PROMIS))
Measure Yourself Medical Outcome Profile (MYMOP) [6 months]
Severity of three subjectively chosen PC19 symptoms
Overall assessment of functional status [6 months]
Severity of PC19 symptom burden
PC19 symptom list [6 months]
checklist, number of subjectively present symptoms
EQ-5D-5L [6 months]
Health related quality of life, 5 point rating scale, 0 to 20 points, higher scores indicate worse outcomes
visual analogue scale [6 months]
Health related quality of life, 0 to 100 points, higher scores indicate a better outcome
PHQ 8 [6 months]
Depression, 4 point rating scale, 0 to 24 points possible, higher scores indicate a worse outcome
Chalder Scale [6 months]
Fatigue, 4 point rating scale, 0 to 33 points possible, higher values 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)
Physical exercise [6 months]
1minute Sit-to-Stand-Test, number of repetitions, BORG Scale, oxygen-saturation
Use of on-demand medication and change in concomitant medication [6 months]
intake of on-demand medication, daily drug doses
qualitative assessment of acceptance [6 months]
qualitative interviews with subgroup sample
feasibility/acceptance [6 months]
exploratory questionnaire, rating scales and grades

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years and Older

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

Inclusion Criteria:

adult patients (at least 18 years old)
history of documented SARS-CoV-2 infection at least 12 weeks ago
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

Exclusion Criteria:

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
hypertension
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 with a possible interaction with the study medication

current or previous systemic treatment with any of the treatment drugs for at least seven days since COVID-19 or any parenteral application
known allergy 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)