AdKCNH2-G628S Gene Therapy for Post-Operative Atrial Fibrillation
Trial Snapshot
- Phase
- Phase 1
- Status
- Withdrawn
- Sponsor
- Enrollment
- 78
- Locations
- 1
- Primary Endpoint
- proportion of patients having a post-operative complication relative to controls
Study Overview
Brief Summary
This clinical trial will have 2 components: a brief dose-ranging study and a randomized comparison of 2 doses of AdKCNH2-G628S with control cardiac surgery patients. The study will assess safety of the intervention in a population at increased risk for post-operative atrial fibrillation.
Detailed Description
Post-operative AF (POAF) is a specific form of AF occurring in the days after cardiothoracic surgery. A unique element of POAF is the limited duration of risk, which peaks 3 days and dissipates 10 days after surgery. We propose gene therapy for POAF. Our hypothesis is that counteracting AF-related electrical remodeling will disrupt the reentrant electrical circuits integral to maintaining AF. We have extensive preclinical data showing safety and efficacy of adenoviral gene transfer using the gene mutation KNCH2-G628S. When delivered to the atria using adenoviruses and a novel gene painting technique, KCNH2-G628S effectively and specifically prolongs atrial action potential and prevents development of AF for the 10-14-day duration of post-operative AF risk. This clinical trial will have 2 components: a brief dose-ranging study and a randomized comparison of 2 doses of AdKCNH2-G628S with control cardiac surgery patients.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Sequential
- Primary Purpose
- Prevention
- Masking
- Triple (Participant, Investigator, Outcomes Assessor)
Masking Description
participant is masked due to delivery during general anesthesia, outcomes assessors and investigators are fully masked to study group.
Eligibility Criteria
- Ages
- 18 Years to — (Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- No
Inclusion Criteria
- Not provided
Exclusion Criteria
- Not provided
Arms & Interventions
dose escalation
initial phase, increasing dose
Intervention: AdKCNH2-G628S (Biological)
low dose
second phase, fixed dose 5x10(11) vp
Intervention: AdKCNH2-G628S (Biological)
high dose
second phase, fixed dose 2x10(12) vp
Intervention: AdKCNH2-G628S (Biological)
Outcomes
Primary Outcomes
proportion of patients having a post-operative complication relative to controls
Time Frame: 3 months
proportion of patients having a post-operative complication relative to controls
Secondary Outcomes
- proportion of patients having post-operative atrial fibrillation(1 month)