Prednisolone and vitamin B1, B6, and B12 in patients with Post-COVID-19-Syndrome (PC19S) – a randomized controlled trial in primary care

INTERVENTION: Trade Name: Vitamin B Komple XForte Product Name: Vitamine B1‐B6‐B12 Pharmaceutical Form: Film‐coated tablet INN or Proposed INN: Thiamine nitrate CAS Number: 532‐43‐4 Concentration unit: mg milligram(s) Concentration number: 100‐ INN or Proposed INN: Pyridoxine hydrochloride CAS Number: 58‐56‐0 Concentration unit: mg milligram(s) Concentration number: 50‐ INN or Proposed INN: Cyanocobalamin CAS Number: 68‐19‐9 Concentration unit: mg milligram(s) Concentration number: 0,5‐ Pharmaceutical form of the placebo: Film‐coated tablet Route of administration of the placebo: Oral use Trade Name: Predni H Tablinen (R) 5mg Product Name: Prednisolone Pharmaceutical Form: Capsule, hard INN or Proposed INN: Prednisolone CAS Number: 50‐24‐8 Concentration unit: mg milligram(s) Concentration number: 5‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use Trade Name: Prednisolon STADA (R) 10mg Product Name: Prednisolone Pharmaceutical Form: Capsule, hard INN or Proposed INN: Prednisolone CAS Number: 50‐24‐8 Concentration unit: mg milligram(s) Concentration number: 20‐ Pharmaceutical form of the placebo: Capsule, hard Route of administration of the placebo: Oral use CONDITION: Post‐COVID‐19‐Syndrome (PC19S) Therapeutic area: Not possible to specify PRIMARY OUTCOME: Main Objective: To assess the effectiveness, safety and feasibility of treating patients with PC19S in primary care with prednisolone and/or vitamin B1, B6, and B12 in a fixed combination. Main objectives are a better understanding of current Post‐COVID care, how it is perceived by patients, and to identify approaches to improve care of these patients. Primary end point(s): The primary outcome of pilot studywill be feasibility and acceptance of screening and recruitment in primary care, as assessed by the retention rate at day 28. ; The primary outcome of confirmatory study will be the change of symptom severity as assessed by a specifically tailored Patient Reported Outcomes Measurement Information Sys‐tem (PROMIS) total score referring to five symptom domains known to be typical for PC19S (fatigue, dyspnoea, cognition, anxiety, depression) from baseline to day 28 Secondary Objective: not applicable Timepoint(s) of evaluation of this end point: Pilot phase: after months 15‐18; Confirmatory phase: after months 21‐24 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 ei‐ther 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’ GP or the local investigator Are the trial subjects under 18? no Number of subjects for this age range: F.1.2 Adults (18‐64 years) yes F.1.2.1 Number of subjects for this age range 270 F.1.3 Elderly (>=65 years) yes F.1.3.1 Number of subjects for this age range 70 SECONDARY OUTCOME: Secondary end point(s): 1. Severity of each PC19 symptom (PROMIS total and subscores in the domains included in the total score, MYMOP; PC19S functional status; PC19 symptom list); 2. Health related quality of life (EQ‐5D‐5L and visual analogue scale); 3. Depression (PHQ 8); 4. Fatigue (Chalder Scale); 5. Pain (numeric rating scale for pain); 6. Cognitive function: Alertness, distractibility, divided attention, flexibility and visual scanning (TAP); 7. Physical exercise (1minute Sit‐to‐Stand‐Test); 8. Use of on‐demand medication and change in concomitant medication (patient diary); 9. feasibility and acceptance (qualitative interviews with subgroup sample; questionnaire) ; 10. physical examination (auscultation of chest lung and heart, orientating neurological examination, check for edema, lymph node status ); Safety will be assessed by AE and SAE. In addition, number of patients with ongoing/worsening symptoms: symptoms at the same level or worse two months after inclusion. Timepoint(s) of evaluation of this end point: Pilot phase: after months 15‐18; Confirmatory phase: after months 21‐24