Summary
Norepinephrine 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 2 registered trials linking Norepinephrine to Atrial Fibrillation: 2 are currently recruiting. The most advanced is Phase 4 (NCT02118467). It plans or enrolled 836 participants. Registration activity spans 2014 to 2021. The literature layer holds 9 publications for this pair: 2 Cochrane reviews, 1 meta-analysis, 1 randomised controlled trial publication and 5 clinical trial publications. Publication years run from 2020 to 2025. 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 | 55.0 (trials 8.0, literature 27.0, tier 15, approved bonus 5.0) |
| Registered trials | 2 total: 2 recruiting, 0 active / not yet recruiting, 0 completed, 0 other |
| Linked publications | 9 (5 clinical trial publications, 2 Cochrane reviews, 1 meta-analysis, 1 randomised controlled trial publication) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | agonist |
| 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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT02118467 | Vasoactive Drugs in Intensive Care Unit 2014 | recruiting | Phase 4 | 836 |
| NCT04844801 | Rate, Rhythm or Risk Control for New-onset Supraventricular Arrhythmia During Septic Shock: a Randomized Controlled Trial 2021 | recruiting | Not applicable | 240 |
Published literature
- Cochrane review Efficacy and Safety of Landiolol in the Treatment of Tachycardia in Patients With Sepsis and Septic Shock: A Systematic Review and Meta-AnalysisPaneer Selvam S, Gamarra-Valverde NN, Tripoli A et al. · Cureus · 2025 · PMID 40821221
- Meta-analysis Does Concomitant Use of Antidepressants and Direct Oral Anticoagulants Increase the Risk of Bleeding?: A Systematic Review and Meta-AnalysisWeng J, Lan R · Journal of clinical psychopharmacology · 2025 · PMID 39836536
- Clinical trial publication Effects of sodium-glucose cotransporter-2 inhibitor on atrial high-rate episodes in patients with cardiovascular implantable electronic device: a randomized controlled trialNantsupawat T, Apaijai N, Phrommintikul A et al. · Scientific reports · 2024 · PMID 39532868
- Clinical trial publication Dexmedetomidine for Reducing Mortality in Patients With Septic Shock: A Randomized Controlled Trial (DecatSepsis)Ezz Al-Regal AR, Ramzy EA, Atia AAA et al. · Chest · 2024 · PMID 39004217
- Clinical trial publication Prospective randomized double-blind study to evaluate the superiority of Vasopressin versus Norepinephrine in the management of the patient at renal risk undergoing cardiac surgery with cardiopulmonary bypass (NOVACC trial)Guinot PG, Desebbe O, Besch G et al. · American heart journal · 2024 · PMID 38492626
- Clinical trial publication Risk factors for poor performance in finger cuff non-invasive monitoring of arterial pressure: A prospective multicenter studyLakhal K, Dauvergne JE, Messet-Charriere H et al. · Anaesthesia, critical care & pain medicine · 2024 · PMID 38048986
- Cochrane review Outcomes of Vasopressin-Receptor Agonists Versus Norepinephrine in Adults With Perioperative Hypotension: A Systematic ReviewHeybati K, Xie G, Ellythy L et al. · Journal of cardiothoracic and vascular anesthesia · 2024 · PMID 38580478
- Clinical trial publication A norepinephrine weaning strategy using dynamic arterial elastance is associated with reduction of acute kidney injury in patients with vasoplegia after cardiac surgery: A post-hoc analysis of the randomized SNEAD studyGuinot PG, Huette P, Bouhemad B et al. · Journal of clinical anesthesia · 2023 · PMID 37099874
- Randomized controlled trial Optimum Blood Pressure in Patients With Shock After Acute Myocardial Infarction and Cardiac ArrestAmeloot K, Jakkula P, Hästbacka J et al. · Journal of the American College of Cardiology · 2020 · PMID 32792079
Mechanism and notes
Recorded mechanism or class: agonist.
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 Norepinephrine approved for Atrial Fibrillation?
Norepinephrine 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 Norepinephrine in clinical trials for Atrial Fibrillation?
ClinicalTrials.gov lists 2 registered trials linking Norepinephrine to Atrial Fibrillation: 2 are currently recruiting. The most advanced is Phase 4 (NCT02118467). It plans or enrolled 836 participants. Registration activity spans 2014 to 2021.
What does the evidence show for Norepinephrine in Atrial Fibrillation?
Trials of Norepinephrine in Atrial Fibrillation are registered but none has completed, so there is no outcome evidence from those studies yet; the record is a signal of research interest. 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.