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Intracoronary Gene Transfer of Adenylyl Cyclase 6 in Patients With Heart Failure A Randomized Clinical Trial
- Source :
- Hammond, HK; Penny, WF; Traverse, JH; Henry, TD; Watkins, M; Yancy, C; et al.(2016). Intracoronary Gene Transfer of Adenylyl Cyclase 6 in Patients With Heart Failure A Randomized Clinical Trial. JAMA CARDIOLOGY, 1(2), 163-171. doi: 10.1001/jamacardio.2016.0008. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/26r0w2kk, JAMA cardiology, vol 1, iss 2
- Publication Year :
- 2016
- Publisher :
- eScholarship, University of California, 2016.
-
Abstract
- ImportanceGene transfer has rarely been tested in randomized clinical trials.ObjectiveTo evaluate the safety and efficacy of intracoronary delivery of adenovirus 5 encoding adenylyl cyclase 6 (Ad5.hAC6) in heart failure.Design, setting, and participantsA randomized, double-blind, placebo-controlled, phase 2 clinical trial was conducted in US medical centers (randomization occurred from July 19, 2010, to October 30, 2014). Participants 18 to 80 years with symptomatic heart failure (ischemic and nonischemic) and an ejection fraction (EF) of 40% or less were screened; 86 individuals were enrolled, and 56 were randomized. Data analysis was of the intention-to-treat population. Participants underwent exercise testing and measurement of left ventricular EF (echocardiography) and then cardiac catheterization, where left ventricular pressure development (+dP/dt) and decline (-dP/dt) were recorded. Participants were randomized (3:1 ratio) to receive 1 of 5 doses of intracoronary Ad5.hAC6 or placebo. Participants underwent a second catheterization 4 weeks later for measurement of dP/dt. Exercise testing and EF were assessed 4 and 12 weeks after randomization.InterventionsIntracoronary administration of Ad5.hAC6 (3.2 × 109 to 1012 virus particles) or placebo.Main outcomes and measuresPrimary end points included exercise duration and EF before and 4 and 12 weeks after randomization and peak rates of +dP/dt and -dP/dt before and 4 weeks after randomization. Fourteen placebo participants were compared (intention to treat) with 24 Ad5.hAC6 participants receiving the highest 2 doses (D4 + 5).ResultsFifty-six individuals were randomized and monitored for up to 1 year. Forty-two participants (75%) received Ad5.hAC6 (mean [SE] age, 63 [1] years; EF, 30% [1%]), and 14 individuals (25%) received placebo (age, 62 [1] years; EF, 30% [2%]). Exercise duration showed no significant group differences (4 weeks, P = .27; 12 weeks, P = .47, respectively). The D4 + 5 participants had increased EF at 4 weeks (+6.0 [1.7] EF units; n = 21; P
- Subjects :
- 0301 basic medicine
Male
Cardiac Catheterization
Left
030204 cardiovascular system & hematology
Cardiovascular
Ventricular Function, Left
law.invention
0302 clinical medicine
Patient Admission
Randomized controlled trial
law
Medicine
Ventricular Function
education.field_of_study
Ejection fraction
Gene Transfer Techniques
Middle Aged
Heart Disease
Treatment Outcome
Echocardiography
6.1 Pharmaceuticals
Cardiology
Female
Cardiology and Cardiovascular Medicine
Adenylyl Cyclases
medicine.medical_specialty
Randomization
Population
Clinical Trials and Supportive Activities
Placebo
Article
Adenoviridae
03 medical and health sciences
Clinical Research
Internal medicine
Humans
education
Aged
Heart Failure
Intention-to-treat analysis
business.industry
Prevention
Evaluation of treatments and therapeutic interventions
Stroke Volume
Genetic Therapy
medicine.disease
United States
Surgery
Clinical trial
030104 developmental biology
Heart failure
Exercise Test
business
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Hammond, HK; Penny, WF; Traverse, JH; Henry, TD; Watkins, M; Yancy, C; et al.(2016). Intracoronary Gene Transfer of Adenylyl Cyclase 6 in Patients With Heart Failure A Randomized Clinical Trial. JAMA CARDIOLOGY, 1(2), 163-171. doi: 10.1001/jamacardio.2016.0008. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/26r0w2kk, JAMA cardiology, vol 1, iss 2
- Accession number :
- edsair.doi.dedup.....22b267ef385efbd6ebf86a0c3943f1fe
- Full Text :
- https://doi.org/10.1001/jamacardio.2016.0008.