| E.1 Medical condition or disease under investigation |
| E.1.1 | Medical condition(s) being investigated |
| Post-COVID-19-Syndrome (PC19S) |
| Post-COVID-19-Syndrom (PC19S) |
|
| E.1.1.1 | Medical condition in easily understood language |
| Post-COVID-19-Syndrome (PC19S) |
| Post-COVID-19-Syndrom (PC19S) |
|
| E.1.1.2 | Therapeutic area | Not possible to specify |
| MedDRA Classification |
| E.1.3 | Condition being studied is a rare disease | No |
| E.2 Objective of the trial |
| E.2.1 | Main objective of the trial |
| 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. |
| Bewertung der Wirksamkeit, Sicherheit und Durchführbarkeit der Behandlung von Patienten mit PC19S in der Primärversorgung mit Prednisolon und/oder Vitamin B1, B6 und B12 in einer festen Kombination. Hauptziele sind ein besseres Verständnis der aktuellen Post-COVID-Versorgung, wie sie von Patienten wahrgenommen wird, und die Identifizierung von Ansätzen zur Verbesserung der Versorgung dieser Patienten. |
|
| E.2.2 | Secondary objectives of the trial |
|
| E.2.3 | Trial contains a sub-study | Yes |
| E.2.3.1 | Full title, date and version of each sub-study and their related objectives |
Patients' perspectives and needs concerning care of Post-COVID.
Substudy is included within mainstudy. Chapter 11.10 |
Perspektiven und Bedarfe in Bezug auf die Gesundheitsversorgung bei Post-COVID
Die Sub-Studie ist in das Protokoll der Hauptstudie integriert. Siehe Kapitel 11.10
|
|
| E.3 | Principal 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
|
|
| E.4 | Principal exclusion criteria |
• acute Coronavirus disease (COVID-19) at baseline visit (rapid SARS-CoV-2 antigen test)
• patients who were treated in the intensive care unit because of COVID-19
• pregnancy/ breastfeeding
• diabetes mellitus
• PC19S symptoms that can be explained by an alternative diagnosis (e.g., chronic fatigue syndrome, depression, active or preceding cancer therapy, severe anemia, sleep apnea syndrome) as assessed by the patients’ GP or the investigator
• 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 [e.g., Chronic Obstructive Pulmonary Disease (COPD), Asthma)
-chronic heart failure [New York Heart Association (NYHA) III and IV]
-neurological disorders
-untreated hypothyroidism
-significantly impaired glucuronidation (e.g., Gilbert-Meulengracht, ROTOR, or Crigler-Najjar syndrome)
-immunodeficiency or a chronically weakened immune system [e.g., ac-quired immunodeficiency syndrome (AIDS), HIV, lymphoma, chemo-radio- therapy, immunosuppressive pathology]
-mental disorders (e.g. depression, psychosis, dementia)
-active cancer
-any other severe medical conditions that preclude participation as deter-mined by responsible physician
• current use of
-immunosuppressive drugs
-non-steroidal antiinflammatory drugs (NSAID), ASS, Indometacin
-fluoroquinolones
-anticoagulation: phenprocoumon or other cumarin derivates, direct oral anticoagulants
-any other drug with a possible interaction that could exhibit clinically relevant inter-actions with the study medication (as described in Fachinformation Prednisolon STADA®, Predni H Tablinen® Zentiva or Fachinformation Vitamin B komplex Hevert). The decision regarding the clinical relevance of the interactions is at the dis-cretion of the principal investigator
• 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 med-ication 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 inclu-sion of the study
• 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) |
|
| E.5 End points |
| E.5.1 | 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 |
|
| E.5.1.1 | Timepoint(s) of evaluation of this end point |
Pilot phase: after months 15-18
Confirmatory phase: after months 21-24 |
|
| E.5.2 | 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. |
|
| E.5.2.1 | Timepoint(s) of evaluation of this end point |
Pilot phase: after months 15-18
Confirmatory phase: after months 21-24 |
|
| E.6 and E.7 Scope of the trial |
| E.6 | Scope of the trial |
| E.6.1 | Diagnosis | No |
| E.6.2 | Prophylaxis | No |
| E.6.3 | Therapy | Yes |
| E.6.4 | Safety | Yes |
| E.6.5 | Efficacy | Yes |
| E.6.6 | Pharmacokinetic | No |
| E.6.7 | Pharmacodynamic | No |
| E.6.8 | Bioequivalence | No |
| E.6.9 | Dose response | No |
| E.6.10 | Pharmacogenetic | No |
| E.6.11 | Pharmacogenomic | No |
| E.6.12 | Pharmacoeconomic | No |
| E.6.13 | Others | No |
| E.7 | Trial type and phase |
| E.7.1 | Human pharmacology (Phase I) | No |
| E.7.1.1 | First administration to humans | No |
| E.7.1.2 | Bioequivalence study | No |
| E.7.1.3 | Other | No |
| E.7.1.3.1 | Other trial type description | |
| E.7.2 | Therapeutic exploratory (Phase II) | No |
| E.7.3 | Therapeutic confirmatory (Phase III) | Yes |
| E.7.4 | Therapeutic use (Phase IV) | No |
| E.8 Design of the trial |
| E.8.1 | Controlled | Yes |
| E.8.1.1 | Randomised | Yes |
| E.8.1.2 | Open | No |
| E.8.1.3 | Single blind | No |
| E.8.1.4 | Double blind | Yes |
| E.8.1.5 | Parallel group | Yes |
| E.8.1.6 | Cross over | No |
| E.8.1.7 | Other | No |
| E.8.2 | Comparator of controlled trial |
| E.8.2.1 | Other medicinal product(s) | No |
| E.8.2.2 | Placebo | Yes |
| E.8.2.3 | Other | No |
| E.8.2.4 | Number of treatment arms in the trial | 4 |
| E.8.3 |
The trial involves single site in the Member State concerned
| No |
| E.8.4 | The trial involves multiple sites in the Member State concerned | Yes |
| E.8.4.1 | Number of sites anticipated in Member State concerned | 3 |
| E.8.5 | The trial involves multiple Member States | No |
| E.8.6 Trial involving sites outside the EEA |
| E.8.6.1 | Trial being conducted both within and outside the EEA | No |
| E.8.6.2 | Trial being conducted completely outside of the EEA | No |
| E.8.7 | Trial has a data monitoring committee | Yes |
| E.8.8 |
Definition of the end of the trial and justification where it is not the last
visit of the last subject undergoing the trial
|
| The end of the study will be reached either after the pilot study if the feasibility is not given or if the data safety monitoring board suggests and the sponsor decides to stop the study prematurely. Otherwise, the study ends when 340 patients have been included and completed the follow up phone call 3 (LVLS). |
|
| E.8.9 Initial estimate of the duration of the trial |
| E.8.9.1 | In the Member State concerned years | 1 |
| E.8.9.1 | In the Member State concerned months | 8 |
| E.8.9.1 | In the Member State concerned days | 0 |
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