Summary
Norepinephrine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Heart Failure would be drug repurposing rather than first-in-human development. This does not mean it is approved for Heart Failure. ClinicalTrials.gov lists 8 registered trials linking Norepinephrine to Heart Failure: 2 are currently recruiting; 2 are active or not yet recruiting; 1 has completed; 3 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 3 (NCT00314704). The largest enrolment is 5000 participants (NCT04682483). Registration activity spans 2003 to 2026. The literature layer holds 13 publications for this pair: 5 Cochrane reviews, 2 meta-analyses, 1 randomised controlled trial publication and 5 clinical trial publications. Publication years run from 2015 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 Heart Failure ranks 616 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: Annual mortality ~22% on standard care; only 5-11% of HFrEF patients achieve normalisation of ejection fraction (HFrecEF) with GDMT; HFpEF has no disease-modifying therapy.
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: 2 recruiting, 2 active / not yet recruiting, 1 completed, 3 other |
| Linked publications | 13 (5 Cochrane reviews, 5 clinical trial publications, 2 meta-analyses, 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 | ADRB3 |
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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT05568160 | Evaluation of the Superiority of VAsopressin Versus NOradrenaline in the Management of Patients at Risk of Kidney Failure Undergoing Cardiac Surgery With Extracorporeal Circulation 2023 | active, not recruiting | Phase 3 | 840 |
| NCT00314704 | Dopamine and Norepinephrine in Shock Patients 2003 | completed | Phase 3 | 1,679 |
| NCT02617602 | Goal Directed Hemodynamic Management of Acute Heart Failure After Cardiac Surgery in Children 2015 | status unknown | Phase 3 | 40 |
| NCT02116140 | ASV Effects on Myocardial Energetics and Sympathetic Nerve Function in Heart Failure and Sleep Apnea. 2012 | active, not recruiting | Not applicable | 60 |
| NCT07286643 | Echocardiography-guided Cirrhosis and Liver Failure-Intensive Care Protocol Sepsis 2026 | recruiting | Not applicable | 140 |
| NCT04682483 | Cardiogenic Shock Working Group Registry 2017 | recruiting | Not applicable | 5,000 |
| NCT05202938 | eMESH Struct. 2022-23 2022 | status unknown | Not applicable | 32 |
| NCT03621618 | Clinical Assessment of Arterial Dynamic Elastance in ICU Patients, Dependent on Inotropic or Vasopressor Drugs. 2019 | withdrawn | Not applicable | — |
Published literature
- Clinical trial publication Effects of dapagliflozin on urinary output, fluid balance, and biochemistry in critically ill patients: a post-hoc secondary analysis of the DEFENDER trialZampieri FG, Azevedo LCP, Neto AS et al. · Critical care (London, England) · 2025 · PMID 40646628
- Clinical trial publication Anaemia predicts iron homoeostasis dysregulation and modulates the response to empagliflozin in heart failure with reduced ejection fraction: the EMPATROPISM-FE trialAngermann CE, Sehner S, Gerhardt LMS et al. · European heart journal · 2025 · PMID 39907687
- Meta-analysis Effects of Renal Denervation on Cardiac Remodeling, Cardiac Function, and Cardiovascular Neurohormones in Heart Failure with Reduced Ejection Fraction Patients: A Meta-Analysis and Systematic ReviewSi F, Liu Q, Ma X et al. · Cardiorenal medicine · 2025 · PMID 40132560
- Clinical trial publication DPP4 (Dipeptidyl Peptidase-4) Inhibition Increases Catecholamines Without Increasing Blood Pressure During Sustained ACE (Angiotensin-Converting Enzyme) Inhibitor TreatmentWilson JR, Garner EM, Mashayekhi M et al. · Hypertension (Dallas, Tex. : 1979) · 2022 · PMID 35045722
- Cochrane review Vasoplegic syndrome after cardiovascular surgery: A review of pathophysiology and outcome-oriented therapeutic managementDatt V, Wadhhwa R, Sharma V et al. · Journal of cardiac surgery · 2021 · PMID 34251716
- Clinical trial publication Empagliflozin in Heart Failure: Diuretic and Cardiorenal EffectsGriffin M, Rao VS, Ivey-Miranda J et al. · Circulation · 2020 · PMID 32410463
- Clinical trial publication Pharmacological Heart Failure Therapy in Children: Focus on Inotropic SupportSchranz D · Handbook of experimental pharmacology · 2020 · PMID 31707469
- Cochrane review Inotropic agents and vasodilator strategies for the treatment of cardiogenic shock or low cardiac output syndromeUhlig K, Efremov L, Tongers J et al. · The Cochrane database of systematic reviews · 2020 · PMID 33152122
- Randomized controlled trial Effects of Cognitive Behavioral Therapy for Insomnia on Sleep, Symptoms, Stress, and Autonomic Function Among Patients With Heart FailureRedeker NS, Conley S, Anderson G et al. · Behavioral sleep medicine · 2020 · PMID 30461315
- Meta-analysis Sympathetic neural overdrive in congestive heart failure and its correlates: systematic reviews and meta-analysisGrassi G, D'Arrigo G, Pisano A et al. · Journal of hypertension · 2019 · PMID 30950979
- Cochrane review Inotropic agents and vasodilator strategies for the treatment of cardiogenic shock or low cardiac output syndromeSchumann J, Henrich EC, Strobl H et al. · The Cochrane database of systematic reviews · 2018 · PMID 29376560
- Cochrane review The Role of Omega-3 Polyunsaturated Fatty Acids in Heart Failure: A Meta-Analysis of Randomised Controlled TrialsWang C, Xiong B, Huang J · Nutrients · 2016 · PMID 28042816
- Cochrane review Antidepressants and cardiovascular adverse events: A narrative reviewNezafati MH, Vojdanparast M, Nezafati P · ARYA atherosclerosis · 2015 · PMID 26715935
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 ADRB3. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Norepinephrine approved for Heart Failure?
Norepinephrine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Heart Failure would be drug repurposing rather than first-in-human development. This does not mean it is approved for Heart Failure. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Norepinephrine in clinical trials for Heart Failure?
ClinicalTrials.gov lists 8 registered trials linking Norepinephrine to Heart Failure: 2 are currently recruiting; 2 are active or not yet recruiting; 1 has completed; 3 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 3 (NCT00314704). The largest enrolment is 5000 participants (NCT04682483). Registration activity spans 2003 to 2026.
What does the evidence show for Norepinephrine in Heart Failure?
Norepinephrine has both completed registered trials and synthesis-level publications linked to Heart Failure. 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 ADRB3. 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.