Summary
Norepinephrine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Sepsis would be drug repurposing rather than first-in-human development. This does not mean it is approved for Sepsis. ClinicalTrials.gov lists 8 registered trials linking Norepinephrine to Sepsis: 4 have completed; 4 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 3 (NCT00314704). It plans or enrolled 1679 participants. Registration activity spans 2003 to 2019. The literature layer holds 16 publications for this pair: 5 Cochrane reviews, 5 meta-analyses, 1 systematic review and 5 clinical trial publications. Publication years run from 2022 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 Sepsis ranks 518 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: Not applicable — sepsis is an acute life-threatening syndrome; hospital mortality 15-25% for sepsis, 30-45% for septic shock with standard care; long-term complications (post-sepsis syndrome) in 50-70% of survivors.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 68.5 (trials 18.5, literature 30.0, tier 15, approved bonus 5.0) |
| Registered trials | 8 total: 0 recruiting, 0 active / not yet recruiting, 4 completed, 4 other |
| Linked publications | 16 (5 Cochrane reviews, 5 meta-analyses, 5 clinical trial publications, 1 systematic review) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | agonist |
| Data sources | DGIdb |
| Linked via biomarker / target | ADRA2C |
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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT02638545 | Hemodynamic Effects of Dexmedetomidine in Septic Shock 2015 | completed | Phase 3 | 37 |
| NCT00314704 | Dopamine and Norepinephrine in Shock Patients 2003 | completed | Phase 3 | 1,679 |
| NCT02069288 | Effects of Fludrocortisone on Norepinephrine-mean Arterial Pressure Dose-response in Septic Shock | withdrawn | Phase 3 | — |
| NCT00527007 | External Cooling in Septic Shock Patients 2007 | completed | Not applicable | 200 |
| NCT00333593 | Super High-Flux - High Volume Dialysis in Sepsis-Induced Acute Renal Failure 2006 | completed | PHASE1, PHASE2 | 10 |
| NCT01473498 | Personalized Mean Arterial Pressure Management on Renal Function During Septic Shock 2013 | terminated | Not applicable | 27 |
| NCT03214913 | Controlled Fluid Resuscitation in Sepsis 2018 | status unknown | Not applicable | 550 |
| 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 The Protective Effect of Vitamin C Targeting Oxidative Stress on Renal Function in Patients with Septic Acute Kidney Injury: A Prospective, Randomized Controlled, Pilot StudyChen Y, Lu M, Shi X et al. · International journal for vitamin and nutrition research. Internationale Zeitschrift fur Vitamin- und Ernahrungsforschung. Journal international de vitaminologie et de nutrition · 2026 · PMID 41873106
- Clinical trial publication Efficacy and Safety of Shenfu Injection in Patients with Septic Shock: A Randomized Controlled Open-Label Trial with Network Pharmacology-Based Mechanistic InsightsHuang P, He SS, Feng S et al. · Chinese journal of integrative medicine · 2026 · PMID 41870792
- Clinical trial publication Clinical and Immunologic Effects of Extracorporeal Cytokine Removal in Patients with Septic Shock: A Randomized Controlled TrialLotz C, Heckelmann J, Lendzian C et al. · Shock (Augusta, Ga.) · 2026 · PMID 41670614
- Clinical trial publication Protective effect of pituitrin combined with norepinephrine on cardiopulmonary injury in patients with septic shock diagnosed by critical care ultrasound evaluationCui H, Yuan X, Lu K et al. · Pakistan journal of pharmaceutical sciences · 2026 · PMID 41620916
- Clinical trial publication Impact of renal vein doppler ultrasound-guided CVP titration in sepsis: a pilot randomized controlled trialHuo Y, Liu MZ, Zhu RY et al. · Critical care (London, England) · 2026 · PMID 41580843
- Meta-analysis Comparison of Esmolol Versus Landiolol on Mortality in Adult Patients With Sepsis: A Systematic Review and Network Meta-AnalysisTang Z, Sun Q, Xu J et al. · Critical care medicine · 2026 · PMID 41363997
- Cochrane review Current and emerging therapeutic options for refractory septic shock: A systematic reviewNacul FE, Bezerra MB, Gomes BC et al. · World journal of critical care medicine · 2025 · PMID 41377532
- Cochrane review Prehospital Interventions, Early Detection, and Their Impact on Survival Outcomes in Patients with Sepsis: A Systematic ReviewBukhari EM, Jurays NS, Alarmati ST et al. · Prehospital emergency care · 2025 · PMID 41334884
- 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
- Cochrane review Influence of hydrocortisone infusion method on the clinical outcome of patients with septic shock: A systematic review and meta-analysisLi Y, Wang Y, Guo J et al. · Journal of intensive medicine · 2025 · PMID 39872840
- Systematic review Interleukin-6 Removal and Clinical Effects of Oxiris: A Systematic Review and Meta-AnalysisUlsamer A, Pomarè Montin D, Bocciero V et al. · Blood purification · 2025 · PMID 40720942
- Cochrane review The Clinical Utility of Targeted Heart Rate Control in Septic Shock: A Systematic Review and Meta-analysis of Randomized Controlled Trials with Trial Sequential AnalysisDatta PK, Sathe P, Roy A et al. · Indian journal of critical care medicine : peer-reviewed, official publication of Indian Society of Critical Care Medicine · 2024 · PMID 39759794
- Meta-analysis The role of esmolol in sepsis: a meta-analysis based on randomized controlled trialsWei Y, Bo F, Wang J et al. · BMC anesthesiology · 2024 · PMID 39266951
- Meta-analysis Comparison of Early and Late Norepinephrine Administration in Patients With Septic Shock: A Systematic Review and Meta-AnalysisAhn C, Yu G, Shin TG et al. · Chest · 2024 · PMID 38972348
- Meta-analysis Continuous renal replacement therapy with the adsorptive oXiris filter may be associated with the lower 28-day mortality in sepsis: a systematic review and meta-analysisWang G, He Y, Guo Q et al. · Critical care (London, England) · 2023 · PMID 37424026
- Meta-analysis Clinical efficacy and safety of vitamin C in the treatment of septic shock patients: systematic review and meta-analysisCai B, Lv X, Lin M et al. · Annals of palliative medicine · 2022 · PMID 35523745
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 ADRA2C. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Norepinephrine approved for Sepsis?
Norepinephrine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Sepsis would be drug repurposing rather than first-in-human development. This does not mean it is approved for Sepsis. Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Norepinephrine in clinical trials for Sepsis?
ClinicalTrials.gov lists 8 registered trials linking Norepinephrine to Sepsis: 4 have completed; 4 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 3 (NCT00314704). It plans or enrolled 1679 participants. Registration activity spans 2003 to 2019.
What does the evidence show for Norepinephrine in Sepsis?
Norepinephrine has both completed registered trials and synthesis-level publications linked to Sepsis. 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 ADRA2C. 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.