Clinical trial NCT05638633: Prednisolone and Vitamin B1/6/12 in Patients With Post-Covid-Syndrome
Official title: Prednisolone and Vitamin B1, B6, and B12 in Patients With Post-COVID-19-Syndrome (PC19S) - a Randomized Controlled Trial in Primary Care
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Post-COVID-19 Syndrome
Keywords: Prednisolone
Vitamin B1
Vitamin B6
Vitamin B12
PC19S
Fatigue
ME/CFS (myalgic encephalomyelitis/chronic fatigue syndrome)
Lead sponsor: Wuerzburg University Hospital
Sponsor class: OTHER
Collaborators: name: University Hospital Tuebingen
name: University Hospital Schleswig-Holstein
First posted: 2022-12-06
Enrollment: 321
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Intervention model description: after Baseline, Randomization to 4 arms:

1. st arm (prednisolone and placebo)
2. nd arm (placebo an Vitamin B compound)
3. rd arm (prednisolone and Vitamin B compound)
4. th arm (placebo and placebo)
Primary purpose: TREATMENT

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.

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)

Primary outcomes:
measure: Pilot phase: Proportion of participants retained after 28 days
timeFrame: 4 weeks
measure: Confirmatory phase: Mean difference in PROMIS Total Score from day 0 to day 28
timeFrame: 4 weeks
Secondary outcomes:
measure: PROMIS total and subscores
timeFrame: 6 months
measure: Measure Yourself Medical Outcome Profile (MYMOP)
timeFrame: 6 months
measure: Overall assessment of functional status
timeFrame: 6 months
measure: PC19 symptom list
timeFrame: 6 months
measure: EQ-5D-5L
timeFrame: 6 months
measure: visual analogue scale
timeFrame: 6 months
measure: PHQ 8
timeFrame: 6 months
measure: Chalder Scale
timeFrame: 6 months
measure: Numeric rating scale for pain
timeFrame: 6 months
measure: Testbatterie zur Aufmerksamkeitsprüfung (TAP)
timeFrame: 4 weeks
measure: Physical exercise
timeFrame: 6 months
measure: Use of on-demand medication and change in concomitant medication
timeFrame: 6 months
measure: qualitative assessment of acceptance
timeFrame: 6 months
measure: feasibility/acceptance
timeFrame: 6 months
Other outcomes:
Locations:
city: Würzburg
country: Germany
facility: University Hospital Wuerzburg
state: Bavaria
city: Kiel
country: Germany
facility: Unversity Hospital Schleswig-Holstein
city: Tuebingen
country: Germany
facility: University Hospital Tuebingen
Study officials:
affiliation: Director of Institute for General Practice Würzburg University Hospital
name: Ildikó Gágyor, Prof. Dr.
role: STUDY_DIRECTOR
References: