BUPROPION HYDROCHLORIDE for Post-COVID syndrome|Post Covid Syndrome (PCS)

Inclusion criteria

• {"criterion_text":"- 1. Male or female patient ≥18 years of age.\n- 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.\n- 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.\n- 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.\n- 3. Fatigue, defined as an FSS (Fatigue Severity Score) ≥45.\n- 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\n- 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\n- 6. Moderate to severe overall disability, defined as a Bell Scale of 20-60.\n- 7. Ability to understand the nature, significance and consequences of the trial and the trial related procedures and to comply with them.\n- 8. Willingness to abstain from changes in the type, dosage, and frequency of concomitant medications through Day 84.\n- 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)."}

Exclusion criteria

• {"criterion_text":"- 1. Known or planned pregnancy or currently breastfeeding\n- 10. Planned abrupt discontinuation of alcohol (from >2 standard drinks per day), benzodiazepines, barbiturates, or antiepileptic drugs during the trial period\n- 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\n- 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\n- 13. Electrolyte imbalance: a) Sodium <130 mmol/L or >150 mmol/L, OR b) Potassium <3.0 mmol/L or >5.5 mmol/L\n- 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)\n- 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)\n- 16. History of suicide attempt within the past 12 months, OR current suicidal ideation (PHQ-9 item 9 score ≥2)\n- 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%\n- 18. Ongoing SARS-CoV-2 infection or positive test for SARS-CoV-2 within 14 days prior to enrolment\n- 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)\n- 2. Known ongoing or planned intake of bupropion-containing products (Zyban®, Elontril®, or any generic bupropion formulation)\n- 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)\n- 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)\n- 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)\n- 23. Patient without legal capacity who is unable to understand the nature, significance, and consequences of the trial\n- 24. Previous enrolment and randomization in this trial\n- 25. Person who is in a relationship of dependence or employment with the sponsor or the investigator\n- 26. Persons deprived of liberty or placed in an institution by judicial or administrative order\n- 27. Any concomitant disease significantly impairing assessment of efficacy endpoints, in the opinion of the investigator\n- 3. Known hypersensitivity or intolerance to bupropion\n- 4. Prior history of Postural Orthostatic Tachycardia Syndrome (POTS) or a persistently elevated resting heart rate above 100 beats per minute\n- 5. Prior history of or ongoing anorexia nervosa, bulimia nervosa, or any malignancy of the central nervous system\n- 6. Prior history of or ongoing epileptic seizures\n- 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\n- 8. Current moderate or severe substance use disorder without documented abstinence for at least 6 months\n- 9. Positive urine drug screen at screening for non-prescribed substances of abuse (amphetamines, cocaine, opioids, benzodiazepines)"}

Primary endpoints

• {"endpoint_text":"- Primary Endpoint (Rank 1): Intra-patient change in intensity of fatigue measured by the FSS total score from Baseline to Day 56\n- 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","definition_or_measurement_approach":"Primary Endpoint (Rank 1): measured as intra-patient change in the Fatigue Severity Scale (FSS) total score from Baseline to Day 56. Primary Endpoint (Rank 2): measured as intra-patient change in SF-36 Physical Function (SF-36-PF) score from Baseline to Day 56; Rank 2 is tested if Rank 1 shows statistical significance (hierarchical testing)."}

Secondary endpoints

• {"endpoint_text":"- 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)\n- 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)\n- Intra-patient change from Baseline to Days 28, 56, and 84 in Depression, anxiety, somatization, and distress symptoms:\n- a)\tSeverity 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)\tSeverity 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)\n- c)\tSeverity 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)\tSeverity 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)\n- Severity of dyspnea measured by the mMRC: a)\tFrom Screening (V1) to Day 28 (V4-MOT, mid-treatment assessment) b)\tFrom Screening (V1) to Day 56 (V5-EOT, end of treatment) c)\tFrom Screening (V1) to Day 84 (V6-EOS, sustained effect 28 days post-treatment)\n- 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)\tFrom Screening (V1) to Day 28 (V4-MOT, mid-treatment assessment) b)\tFrom Screening (V1) to Day 56 (V5-EOT, end of treatment)\n- Cognitive function measured by the Symbol Digit Modalities Test (SDMT): a)\tFrom Screening (V1) to Day 28 (V4-MOT, mid-treatment assessment) b)\tFrom Screening (V1) to Day 56 (V5-EOT, end of treatment)\n- 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: •\tSerum •\tEDTA-Plasma •\tPBMCs (Heparin blood) •\tCytometry / CyTOF (Heparin blood)","definition_or_measurement_approach":"Secondary endpoints are measured by the named validated instruments and timepoints: SF-36-PF, FSS, PHQ-9, GAD-7, PHQ-15, PHQ-stress, mMRC, 1-Minute Sit-to-Stand Test (1MSTS), SDMT; times specified (Screening, Day 28, Day 56, Day 84) as per endpoint descriptions. Exploratory biosamples collected at Baseline, Day 1 and Day 56 with specified sample types and total volumes."}

Other endpoints

• {"endpoint_text":"- 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: •\tSerum •\tEDTA-Plasma •\tPBMCs (Heparin blood) •\tCytometry / CyTOF (Heparin blood)","definition_or_measurement_approach":"Biosample collection described for future stratification; samples collected at Baseline, Day 1 and Day 56; total 45 mL at both visits, divided into serum, EDTA-plasma, PBMCs and cytometry/CyTOF samples."}

Germany

Earliest CTIS Part Ii Submission Date

25-03-2026

Latest Decision Or Authorization Date

08-05-2026

Processing Time Days

44

Number Of Sites

11

Number Of Participants

250

Primary sponsor

Full Name

Goethe University Frankfurt

Organisation Type

Educational Institution

Country Of Registered Address

Germany

Third parties

• {"country":"","full_name":"Bundesministerium für Forschung, Technologie und Raumfahrt (BMFTR)","duties_or_roles":"Monetary support","organisation_type":""}