Using smallpox vaccine to prevent monkeypox after exposure

SMART (Smallpox Vaccine for Mpox Post-Exposure Prophylaxis: A Cluster Randomized Controlled Trial)

Phase 4 Interventional McMaster University · NCT05745987

This study is testing if the smallpox vaccine can help prevent monkeypox and reduce symptoms in people who have been exposed to the virus.

Quick facts

PhasePhase 4
Study typeInterventional
Enrollment3000 (estimated)
Ages2 Years and up
SexAll
SponsorMcMaster University Academic / other
Locations10 sites (Kinshasa, Bukavu and 9 other locations)
Trial IDNCT05745987 on ClinicalTrials.gov

What this trial studies

This is a cluster randomized controlled trial designed to evaluate the effectiveness of the smallpox vaccine in reducing the incidence of monkeypox and alleviating symptom severity among individuals exposed to the virus. Households with at least one confirmed case of monkeypox will be randomly assigned to receive either the smallpox vaccine or a control treatment. The study aims to measure the rate of RT-PCR confirmed monkeypox cases and the severity of symptoms as co-primary outcomes. The trial is pragmatic and adaptive, allowing for real-world applicability of the findings.

Who should consider this trial

Good fit: Ideal candidates include household members of individuals with laboratory-confirmed monkeypox who are at least 2 years old and within 14 days of the onset of illness in the index case.

Not a fit: Patients who are pregnant, breastfeeding, have a history of serious allergic reactions to the vaccine components, or have previously received a smallpox vaccination may not benefit from this study.

Why it matters

Potential benefit: If successful, this approach could significantly reduce the spread of monkeypox and improve outcomes for those exposed to the virus.

How similar studies have performed: Other studies have shown promise in using smallpox vaccination strategies for similar viral outbreaks, indicating potential for success in this approach.

Eligibility criteria

Show full inclusion / exclusion criteria
Inclusion Criteria:

1. Household member of person with laboratory confirmed mpox
2. Age ≥ 2 years
3. Within 14 days of onset of illness in mpox index case

Exclusion Criteria:

1. Pregnancy
2. Breastfeeding
3. Past serious allergic reaction to study vaccine components
4. Previous smallpox vaccination
5. Current or planned use of another investigational drug at any point during study participation

Where this trial is running

Kinshasa, Bukavu and 9 other locations

Study contacts

How to participate

  1. Review the eligibility criteria above with your treating physician.
  2. Visit the official trial page on ClinicalTrials.gov for the most current contact information and recruitment status.
  3. Contact the listed study coordinator or principal investigator to request pre-screening. Pre-screening is free and never obligates you to enroll.
Conditions Monkeypoxmpox
Last reviewed 2026-06-09 by the Find a Trial editorial team. Information on this page is for educational purposes and is not medical advice. Always consult qualified healthcare professionals about clinical trial participation.