Summary
Propafenone has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Atrial Fibrillation would be drug repurposing rather than first-in-human development. This does not mean it is approved for Atrial Fibrillation. ClinicalTrials.gov lists 8 registered trials linking Propafenone to Atrial Fibrillation: 1 is currently recruiting; 1 is active or not yet recruiting; 2 have completed; 4 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT05720572). The largest enrolment is 1746 participants (NCT05293080). Registration activity spans 2006 to 2025. The literature layer holds 13 publications for this pair: 5 Cochrane reviews, 3 meta-analyses and 5 clinical trial publications. Publication years run from 2021 to 2026. Because at least one synthesis-level source exists (systematic review, meta-analysis or Cochrane review), this pair has been assessed beyond single studies, although the synthesis may concern a different indication.
The RepurpOS disease-intelligence file for Atrial Fibrillation ranks 332 candidate therapeutics from Open Targets, ChEMBL, DGIdb and PubMed; only a minority carry direct clinical evidence, and this page covers one of those. Spontaneous remission context recorded for the condition: Spontaneous reversion to sinus rhythm occurs in ~50% of paroxysmal AF within 24-48 hours; persistent AF almost never self-terminates; rate-control (the dominant strategy) by definition keeps the patient in AF.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 73.0 (trials 23.0, literature 30.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 1 recruiting, 1 active / not yet recruiting, 2 completed, 4 other |
| Linked publications | 13 (5 Cochrane reviews, 5 clinical trial publications, 3 meta-analyses) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | inhibitor |
| Data sources | DGIdb |
| Linked via biomarker / target | ADRB2 |
How the evidence score is calculated
- Each registered trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5). The trial component is capped at 30.
- Each literature item scores by design (Cochrane review 5, meta-analysis 4, systematic review 3, RCT 3, clinical trial publication 2, curated reference 1.5, other PubMed record 1). The literature component is capped at 30.
- The existing evidence tier adds 15 (A / Strong), 10 (B / Moderate), 5 (C / Preliminary) or 0 (D / Anecdotal).
- Agents approved for any indication (max clinical phase 4) add 5, because an approved agent has an established safety profile that lowers the barrier to repurposing trials.
- The score ranks what has been studied, not what works. It does not read effect sizes or directions of effect.
Registered clinical trials
| NCT ID | Title | Status | Phase | Enrolment |
|---|---|---|---|---|
| NCT05720572 | Antazoline in Comparison to Propafenone in Pharmacological Cardioversion of Atrial Fibrillation. 2019 | status unknown | Phase 4 | 105 |
| NCT00523978 | A Clinical Study of the Arctic Front Cryoablation Balloon for the Treatment of Paroxysmal Atrial Fibrillation 2006 | completed | Phase 3 | 245 |
| NCT05939076 | First-line Cryoablation for Early Treatment of Persistent Atrial Fibrillation 2023 | not yet recruiting | Phase 3 | 220 |
| NCT05293080 | Early Treatment of Atrial Fibrillation for Stroke Prevention Trial in Acute STROKE 2025 | recruiting | Phase 3 | 1,746 |
| NCT00392106 | High Intensity Focused Ultrasound (HIFU) Ablation System Study 2006 | suspended | Phase 3 | 240 |
| NCT03437356 | Pulmonary Vein Isolation With Versus Without Continued Antiarrhythmic Drugs in Persistent Atrial Fibrillation 2018 | completed | Not applicable | 210 |
| NCT02710669 | New Formulations of Propafenone to Treat Atrial Fibrillation 2016 | terminated | PHASE1, PHASE2 | 193 |
| NCT05514860 | The Impact of "First-Line" Rhythm Therapy on AF Progression 2017 | status unknown | Not applicable | 303 |
Published literature
- Meta-analysis Analysis of randomized controlled studies comparing ablation with antiarrhythmic drugsAlhourani N, Ellermann C, Wolfes J et al. · Trends in cardiovascular medicine · 2026 · PMID 40803485
- Cochrane review Safety and Effectiveness of Antidysrhythmic Drugs for Pharmacologic Cardioversion of Recent-Onset Atrial Fibrillation: a Systematic Review and Bayesian Network Meta-analysisdeSouza IS, Shrestha P, Allen R et al. · Cardiovascular drugs and therapy · 2025 · PMID 38324103
- Clinical trial publication Echocardiography predictors of sustained sinus rhythm after cardioversion of supraventricular arrhythmia in patients with septic shockBalik M, Waldauf P, Maly M et al. · Journal of critical care · 2024 · PMID 38759581
- Clinical trial publication Safety and efficacy of long-term sodium channel blocker therapy for early rhythm control: the EAST-AFNET 4 trialRillig A, Eckardt L, Borof K et al. · Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2024 · PMID 38702961
- Clinical trial publication The outcomes of patients with septic shock treated with propafenone compared to amiodarone for supraventricular arrhythmias are related to end-systolic left atrial volumeWaldauf P, Porizka M, Horejsek J et al. · European heart journal. Acute cardiovascular care · 2024 · PMID 38372622
- Clinical trial publication Efficacy and safety of antazoline vs propafenone for conversion of paroxysmal atrial fibrillation to sinus rhythm: a randomized, double-blind study (AnProAF)Karwowski J, Wrzosek K, Mączyńska-Mazuruk R et al. · Polish archives of internal medicine · 2024 · PMID 38166357
- Cochrane review External electrical and pharmacological cardioversion for atrial fibrillation, atrial flutter or atrial tachycardias: a network meta-analysisKukendrarajah K, Ahmad M, Carrington M et al. · The Cochrane database of systematic reviews · 2024 · PMID 38828867
- Clinical trial publication Propafenone versus amiodarone for supraventricular arrhythmias in septic shock: a randomised controlled trialBalik M, Maly M, Brozek T et al. · Intensive care medicine · 2023 · PMID 37698594
- Cochrane review Effect of Early Pharmacologic Cardioversion vs. Non-early Cardioversion in the Patients With Recent-Onset Atrial Fibrillation Within 4-Week Follow-Up Period: A Systematic Review and Network Meta-AnalysisTang Y, Wang Y, Sun X et al. · Frontiers in cardiovascular medicine · 2022 · PMID 35479281
- Cochrane review Reappraising the role of class Ic antiarrhythmics in atrial fibrillationTsiachris D, Doundoulakis I, Tsioufis P et al. · European journal of clinical pharmacology · 2022 · PMID 35190869
- Cochrane review Comparative efficacy and safety of wenxin granule combined with antiarrhythmic drugs for atrial fibrillation: A protocol for a systematic review and network meta-analysisShi S, Chu Y, Jia Q et al. · Medicine · 2021 · PMID 33546090
- Meta-analysis Single-dose oral anti-arrhythmic drugs for cardioversion of recent-onset atrial fibrillation: a systematic review and network meta-analysis of randomized controlled trialsIbrahim OA, Belley-Côté EP, Um KJ et al. · Europace : European pacing, arrhythmias, and cardiac electrophysiology : journal of the working groups on cardiac pacing, arrhythmias, and cardiac cellular electrophysiology of the European Society of Cardiology · 2021 · PMID 33723602
- Meta-analysis Pharmacologic Cardioversion in Patients with Paroxysmal Atrial Fibrillation: A Network Meta-AnalysisTsiachris D, Doundoulakis I, Pagkalidou E et al. · Cardiovascular drugs and therapy · 2021 · PMID 33400054
Mechanism and notes
Recorded mechanism or class: inhibitor.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target ADRB2. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Propafenone approved for Atrial Fibrillation?
Propafenone has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Atrial Fibrillation would be drug repurposing rather than first-in-human development. This does not mean it is approved for Atrial Fibrillation. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Propafenone in clinical trials for Atrial Fibrillation?
ClinicalTrials.gov lists 8 registered trials linking Propafenone to Atrial Fibrillation: 1 is currently recruiting; 1 is active or not yet recruiting; 2 have completed; 4 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 4 (NCT05720572). The largest enrolment is 1746 participants (NCT05293080). Registration activity spans 2006 to 2025.
What does the evidence show for Propafenone in Atrial Fibrillation?
Propafenone has both completed registered trials and synthesis-level publications linked to Atrial Fibrillation. That is the strongest profile in this database, but the summaries here do not extract effect sizes, so read the linked reviews for direction and magnitude of benefit. OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in DGIdb, in this case via the biomarker or target ADRB2. The tier describes how well the drug-disease link is documented, not how well the drug works.
Cite this page
Data: ClinicalTrials.gov, PubMed, Open Targets, ChEMBL, DGIdb and the OSMF therapeutic agent database. Last updated 2026-07-05. Page built 2026-10-07.