The RAPID-Elapse study: Can the drug bupropion improve fatigue symptoms in patients with long COVID?

Overview

Sponsor-declared trial summary

Key facts

Sponsor

Goethe University Frankfurt

Participant type

Patients

Age range

18-64 years, 65+ years

Gender

Male and Female

Therapeutic area

Diseases [C] - Virus Diseases [C02], Diseases [C] - Respiratory Tract Diseases [C08]

Decision date (initial)

2026-04-13

Transition trial

No

Low-intervention

No

Rare-disease indication

No

Vulnerable population

No

Funding sources

Bundesministerium für Forschung, Technologie und Raumfahrt (BMFTR)

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Safety, Efficacy, Therapy

The primary objectives of the RAPID_ELAPSE trial are hierarchically structured to evaluate the efficacy of bupropion against placebo. The highest priority is to measure the improvement in fatigue severity and incapacitation, assessed by the intra-patient change in the total score of the Fatigue Severity Scale (FSS). Should this endpoint show statistical significance, the analysis proceeds to the second primary objective: assessing the change in the patient's overall physical function using the Short Form-36 Physical Function (SF-36-PF) score.

Conditions and MedDRA coding

Post Covid Syndrome (PCS)

Regulatory references

Plan to share IPD

No

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 11

1. 1. Male or female patient ≥18 years of age.
2. 2. Proof of SARS-CoV-2 infection (confirmed by PCR, antigen test, or structured assessment with signed attestation for undocumented positive antigen tests) ≥3 months prior.
3. 3. Fatigue, defined as an FSS (Fatigue Severity Score) ≥45.
4. 4. At least one additional post-COVID symptom, defined as: a) shortness of breath, defined as a mMRC ≥2 b) reduced exercise capacity, defined as <29 repetitions during the 1MSTST c) cognitive impairment, defined as a score of <44 on the written version of the SDMT d) Post-exertional malaise, defined as PEM-Screening positive
5. 5. Symptom persistence and exclusion of alternative diagnosis: a) Symptoms from inclusion criteria 3 (fatigue) AND 4 (at least one additional symptom) must have persisted for ≥3 months after the initial SARS-CoV-2 infection b) No alternative diagnosis has been identified that better explains the presenting symptoms
6. 6. Moderate to severe overall disability, defined as a Bell Scale of 20-60.
7. 7. Ability to understand the nature, significance and consequences of the trial and the trial related procedures and to comply with them.
8. 8. Willingness to abstain from changes in the type, dosage, and frequency of concomitant medications through Day 84.
9. 9. Use of a highly effective method of contraception correctly and consistently, as applicable, during trial treatment and for 30 days after the final dose (applicable to individuals of childbearing potential and participating men whose partners may become pregnant).
10. 10. Female patients of childbearing potential, must have a negative pregnancy test at Screening AND agreement of not to attempt to become pregnant AND agreement of not to donate ova AND usage of highly effective forms of birth control.
11. 11. Male patients with female partners of childbearing potential must agree to use adequate barrier contraception (condoms) during treatment with the IMP and for 30 days following the last dose of study medication.

Exclusion criteria 27

1. 1. Known or planned pregnancy or currently breastfeeding
2. 2. Known ongoing or planned intake of bupropion-containing products (Zyban®, Elontril®, or any generic bupropion formulation)
3. 3. Known hypersensitivity or intolerance to bupropion
4. 4. Prior history of Postural Orthostatic Tachycardia Syndrome (POTS) or a persistently elevated resting heart rate above 100 beats per minute
5. 5. Prior history of or ongoing anorexia nervosa, bulimia nervosa, or any malignancy of the central nervous system
6. 6. Prior history of or ongoing epileptic seizures
7. 7. Concurrent use of prohibited medications: a) Monoamine oxidase inhibitors (MAOIs): phenelzine, tranylcypromine, selegiline, rasagiline, isocarboxazid, linezolid, methylene blue IV b) Other bupropion-containing products: Zyban®, Elontril®, or any generic bupropion formulation c) Selective serotonergic drugs: SSRIs (e.g., sertraline, fluoxetine, paroxetine, citalopram, escitalopram), SNRIs (e.g., venlafaxine, duloxetine, desvenlafaxine) d) Drugs metabolized by or influencing CYP2D6: tamoxifen, antiarrhythmics (flecainide, propafenone), beta-blockers (metoprolol, carvedilol, timolol), antipsychotics (risperidone, aripiprazole, perphenazine), codeine, tramadol, dextromethorphan, atomoxetine, efavirenz, ritonavir, clopidogrel, ticlopidine e) Drugs lowering seizure threshold: antipsychotics (clozapine, olanzapine, quetiapine, haloperidol, chlorpromazine), quinolone antibiotics (ciprofloxacin, levofloxacin, moxifloxacin), tramadol and tapentadol, sedating antihistamines (diphenhydramine, high-dose hydroxyzine), tricyclic antidepressants (amitriptyline, imipramine), antimalarials (chloroquine, mefloquine), theophylline, high-dose systemic corticosteroids, stimulants (methylphenidate, amphetamines) f) Prohibited medications must be discontinued ≥14 days prior to enrolment
8. 8. Current moderate or severe substance use disorder without documented abstinence for at least 6 months
9. 9. Positive urine drug screen at screening for non-prescribed substances of abuse (amphetamines, cocaine, opioids, benzodiazepines)
10. 10. Planned abrupt discontinuation of alcohol (from >2 standard drinks per day), benzodiazepines, barbiturates, or antiepileptic drugs during the trial period
11. 11. Hepatic impairment: a) Severe liver cirrhosis (Child-Pugh Class C), OR b) ALT or AST >3× ULN at screening, OR c) Total bilirubin >2× ULN at screening (excluding Gilbert's syndrome), OR d) ALT or AST >3× ULN with total bilirubin >1.5× ULN
12. 12. Renal impairment: a) eGFR <30 mL/min/1.73 m² (CKD stage 4-5) at screening (calculated using CKD-EPI equation), OR b) End-stage renal disease requiring hemodialysis or peritoneal dialysis, OR c) Serum creatinine increase ≥2-fold from baseline within 7 days prior to screening, OR d) Acute decline in renal function requiring urgent intervention
13. 13. Electrolyte imbalance: a) Sodium <130 mmol/L or >150 mmol/L, OR b) Potassium <3.0 mmol/L or >5.5 mmol/L
14. 14. Uncontrolled hypertension: Systolic BP ≥160 mmHg and/or diastolic BP ≥100 mmHg at screening (average of ≥2 measurements after 5 minutes of rest, on two separate occasions if initial reading elevated)
15. 15. Active major psychiatric illness that cannot be adequately controlled, defined as: a) Schizophrenia, schizoaffective disorder, or depression with psychotic features (psychiatric hospitalization within past 12 months, OR dose adjustment of antipsychotic within past 3 months, OR current active hallucinations or delusions), OR b) Bipolar disorder (psychiatric hospitalization for mania/hypomania within past 12 months, OR dose adjustment of mood stabilizer within past 3 months, OR current manic/hypomanic/mixed episode), OR c) Severe depression (PHQ-9 >25 with psychiatric hospitalization within past 6 months, OR initiation/dose adjustment of antidepressant within past 6 weeks, OR clinical deterioration requiring urgent psychiatric intervention)
16. 16. History of suicide attempt within the past 12 months, OR current suicidal ideation (PHQ-9 item 9 score ≥2)
17. 17. Severe cardiovascular disease: a) Severe heart failure (NYHA Class III-IV), OR b) Clinically significant arrhythmias (uncontrolled atrial fibrillation with ventricular rate >100 bpm, documented ventricular tachycardia/fibrillation, requiring antiarrhythmic medication or cardiac device), OR c) QTc prolongation (>480 ms on screening ECG), OR d) Brugada syndrome, OR e) Recent myocardial infarction (within past 6 months), OR f) Unstable angina (angina at rest or with minimal activity, new-onset severe angina within 2 months, crescendo angina, or hospitalization for angina within past 3 months), OR g) Cardiomyopathy with LVEF <40%
18. 18. Ongoing SARS-CoV-2 infection or positive test for SARS-CoV-2 within 14 days prior to enrolment
19. 19. Evidence of currently active malignancy (primary tumor or metastases) of any organ system (excluding localized basal cell carcinoma of the skin or adequately treated cervical cancer)
20. 20. Pre-COVID history of chronic fatigue syndrome (CFS/ME) or other fatigue syndromes due to associated diseases (e.g., cancer-related fatigue, autoimmune disease-associated fatigue)
21. 21. Participation in any other interventional clinical trial within 30 days before the start of this trial (or 5 half-lives of the investigational product, whichever is longer)
22. 22. Simultaneous participation in other interventional trials which could interfere with this trial (Note: simultaneous participation in non-interventional registry and diagnostic trials is permitted)
23. 23. Patient without legal capacity who is unable to understand the nature, significance, and consequences of the trial
24. 24. Previous enrolment and randomization in this trial
25. 25. Person who is in a relationship of dependence or employment with the sponsor or the investigator
26. 26. Persons deprived of liberty or placed in an institution by judicial or administrative order
27. 27. Any concomitant disease significantly impairing assessment of efficacy endpoints, in the opinion of the investigator

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 2

1. Primary Endpoint (Rank 1): Intra-patient change in intensity of fatigue measured by the FSS total score from Baseline to Day 56
2. Primary Endpoint (Rank 2): Intra-patient change in physical function as measured by the Short Form-36 Physical Function (SF-36-PF) from Baseline to Day 56

Secondary endpoints 9

1. Intra-patient change in physical function as measured by the SF-36-PF from Baseline to: a) Day 28 (V4-MOT, mid-treatment assessment) b) Day 84 (V6-EOS, sustained effect 28 days post-treatment)
2. Intra-patient change in intensity of fatigue as measured by the FSS: a) From Screening (V1) to Day 28 (V4-MOT, mid-treatment assessment) b) From Screening (V1) to Day 84 (V6-EOS, sustained effect 28 days post-treatment)
3. Intra-patient change from Baseline to Days 28, 56, and 84 in Depression, anxiety, somatization, and distress symptoms:
4. a) Severity of depression measured by PHQ-9: from Baseline (V2, Day 1) to Day 28 (V4-MOT), Day 56 (V5-EOT), and Day 84 (V6-EOS) b) Severity of generalized anxiety measured by GAD-7: from Baseline (V2, Day 1) to Day 28 (V4-MOT), Day 56 (V5-EOT), and Day 84 (V6-EOS)
5. c) Severity of somatic symptoms measured by PHQ-15: from Baseline (V2, Day 1) to Day 28 (V4-MOT), Day 56 (V5-EOT), and Day 84 (V6-EOS) d) Severity of psychosocial strain measured by PHQ-stress: from Baseline (V2, Day 1) to Day 28 (V4-MOT), Day 56 (V5-EOT), and Day 84 (V6-EOS)
6. Severity of dyspnea measured by the mMRC: a) From Screening (V1) to Day 28 (V4-MOT, mid-treatment assessment) b) From Screening (V1) to Day 56 (V5-EOT, end of treatment) c) From Screening (V1) to Day 84 (V6-EOS, sustained effect 28 days post-treatment)
7. Intra-patient change from Screening to Days 28 and 56 in: Physical exercise capacity measured by the 1-Minute Sit-to-Stand Test (1MSTS): a) From Screening (V1) to Day 28 (V4-MOT, mid-treatment assessment) b) From Screening (V1) to Day 56 (V5-EOT, end of treatment)
8. Cognitive function measured by the Symbol Digit Modalities Test (SDMT): a) From Screening (V1) to Day 28 (V4-MOT, mid-treatment assessment) b) From Screening (V1) to Day 56 (V5-EOT, end of treatment)
9. Exploratory Endpoints: Biosample collection for future patient stratification: The following materials will be collected at Baseline, Day 1, and Day 56. At both visits, a total volume of 45 mL will be drawn, divided as follows: • Serum • EDTA-Plasma • PBMCs (Heparin blood) • Cytometry / CyTOF (Heparin blood)

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 1

Placebo 1

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

Goethe University Frankfurt

Sponsor organisation

Goethe University Frankfurt

Address

Theodor-Stern-Kai 7

City

Frankfurt Am Main

Postcode

60590

Country

Germany

Scientific contact point

Organisation

Goethe University Frankfurt

Contact name

Maria J.G.T. Vehreschild

Public contact point

Organisation

Goethe University Frankfurt

Contact name

Maria J.G.T. Vehreschild

Locations

1 EU/EEA country · 11 investigational sites

By country

Investigational sites

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 21 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

Application history

2 submissions — initial application plus substantial / non-substantial modifications