Summary
Nicotine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Peripheral Artery Disease (PAD) would be drug repurposing rather than first-in-human development. This does not mean it is approved for Peripheral Artery Disease (PAD). ClinicalTrials.gov lists 4 registered trials linking Nicotine to Peripheral Artery Disease (PAD): 2 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 3 (NCT00461630). It plans or enrolled 25673 participants. Registration activity spans 2007 to 2023. The literature layer holds 8 publications for this pair: 2 Cochrane reviews, 2 systematic reviews and 4 clinical trial publications. Publication years run from 2003 to 2024. 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 Peripheral Arterial Disease ranks 292 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: Progressive disease; spontaneous improvement rare; limb ischaemia worsens in 25-30% over 5 years; major adverse limb events (MALE) in 10-15%/year in advanced PAD; major amputation in 5-10% at 5 years without revascularisation.
Evidence table
| Evidence tier | A · Strong |
|---|---|
| Evidence score | 52.5 (trials 8.5, literature 24.0, tier 15, approved bonus 5.0) |
| Registered trials | 4 total: 0 recruiting, 0 active / not yet recruiting, 2 completed, 2 other |
| Linked publications | 8 (4 clinical trial publications, 2 Cochrane reviews, 2 systematic reviews) |
| Agent type | Drug (Small molecule) |
| Development stage (any indication) | Approved |
| Mechanism / class | Not recorded |
| Data sources | Open Targets, ChEMBL |
| Linked via biomarker / target | ABO |
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trial scores by status (recruiting / active / enrolling 3, completed 2.5, not yet recruiting 2, unknown 1, terminated / withdrawn / suspended 0.5) plus a phase bonus (phase 3-4 +2, phase 2 +1, phase 1 +0.5).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 |
|---|---|---|---|---|
| NCT00461630 | Treatment of HDL to Reduce the Incidence of Vascular Events HPS2-THRIVE 2007 | completed | Phase 3 | 25,673 |
| NCT02220686 | Vascular Physician Offer and Report (VAPOR) Trial 2014 | completed | Not applicable | 156 |
| NCT05469698 | Onsite Tobacco Cessation Treatment for Patients With PAD 2022 | status unknown | Not applicable | 15 |
| NCT05566678 | Effect of Switching From Cigarette Smoking to THS on Systemic Endothelial Function in Subjects With Established Atherosclerotic Disease 2023 | withdrawn | Not applicable | — |
Published literature
- Clinical trial publication Switching to E-cigarettes as Harm Reduction Among Individuals With Chronic Disease Who Currently Smoke: Results of a Pilot Randomized Controlled TrialVojjala M, Stevens ER, Nicholson A et al. · Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2024 · PMID 38995184
- Clinical trial publication Feasibility and pilot efficacy of a brief smoking cessation intervention delivered by vascular surgeons in the Vascular Physician Offer and Report (VAPOR) TrialGoodney PP, Spangler EL, Newhall K et al. · Journal of vascular surgery · 2017 · PMID 28190719
- Clinical trial publication Impact and Duration of Brief Surgeon-Delivered Smoking Cessation Advice on Attitudes Regarding Nicotine Dependence and Tobacco Harms for Patients with Peripheral Arterial DiseaseNewhall K, Suckow B, Spangler E et al. · Annals of vascular surgery · 2017 · PMID 27521828
- Systematic review Hormonal contraception among electronic cigarette users and cardiovascular risk: a systematic reviewRiley HE, Berry-Bibee E, England LJ et al. · Contraception · 2016 · PMID 26546021
- Systematic review [Recent Knowledge of Smoking and Peripheral Arterial Disease in Lower Extremities]Sotoda Y, Hirooka S, Orita H et al. · Nihon eiseigaku zasshi. Japanese journal of hygiene · 2015 · PMID 26411939
- Clinical trial publication Smoking cessation may not improve quality of life in atherosclerotic patientsWiggers LC, Oort FJ, Peters RJ et al. · Nicotine & tobacco research : official journal of the Society for Research on Nicotine and Tobacco · 2006 · PMID 16920656
- Cochrane review Medical treatment of peripheral arterial diseaseHankey GJ, Norman PE, Eikelboom JW · JAMA · 2006 · PMID 16449620
- Cochrane review Smoking cessation strategies in patients with peripheral arterial disease: an evidence-based approachHobbs SD, Bradbury AW · European journal of vascular and endovascular surgery : the official journal of the European Society for Vascular Surgery · 2003 · PMID 14511993
Mechanism and notes
No mechanism of action is recorded for this pair in the source databases.
OSMF's existing evidence tier for this pair is A (Strong), derived from the strength of the disease association recorded in Open Targets and ChEMBL, in this case via the biomarker or target ABO. The tier describes how well the drug-disease link is documented, not how well the drug works.
Frequently asked questions
Is Nicotine approved for Peripheral Artery Disease (PAD)?
Nicotine has reached the approved stage (maximum clinical phase 4) for at least one indication, so its use in Peripheral Artery Disease (PAD) would be drug repurposing rather than first-in-human development. This does not mean it is approved for Peripheral Artery Disease (PAD). Approval status for the specific indication should always be confirmed with the relevant regulator and prescribing information.
Is Nicotine in clinical trials for Peripheral Artery Disease (PAD)?
ClinicalTrials.gov lists 4 registered trials linking Nicotine to Peripheral Artery Disease (PAD): 2 have completed; 2 are terminated, withdrawn, suspended or of unknown status. The most advanced is Phase 3 (NCT00461630). It plans or enrolled 25673 participants. Registration activity spans 2007 to 2023.
What does the evidence show for Nicotine in Peripheral Artery Disease (PAD)?
Nicotine has both completed registered trials and synthesis-level publications linked to Peripheral Artery Disease (PAD). 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 Open Targets and ChEMBL, in this case via the biomarker or target ABO. 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.