Abstract | BACKGROUND: METHODS AND RESULTS: Thirty-nine patients received intracoronary adeno-associated virus type 1/ sarcoplasmic reticulum Ca(2+)-ATPase or placebo. Seven efficacy parameters were assessed in 4 domains: symptoms (New York Heart Association class, Minnesota Living With Heart Failure Questionnaire), functional status (6-minute walk test, peak maximum oxygen consumption), biomarker (N-terminal prohormone brain natriuretic peptide), and left ventricular function/ remodeling (left ventricular ejection fraction, left ventricular end-systolic volume), plus clinical outcomes. The primary end point success criteria were prospectively defined as achieving efficacy at 6 months in the group-level (concordant improvement in 7 efficacy parameters and no clinically significant worsening in any parameter), individual-level (total score for predefined clinically meaningful changes in 7 efficacy parameters), or outcome end points (cardiovascular hospitalizations and time to terminal events). Efficacy in 1 analysis had to be associated with at least a positive trend in the other 2 analyses. This combination of requirements resulted in a probability of success by chance alone of 2.7%. The high-dose group versus placebo met the prespecified criteria for success at the group-level, individual-level, and outcome analyses (cardiovascular hospitalizations) at 6 months (confirmed at 12 months) and demonstrated improvement or stabilization in New York Heart Association class, Minnesota Living With Heart Failure Questionnaire, 6-minute walk test, peak maximum oxygen consumption, N-terminal prohormone brain natriuretic peptide levels, and left ventricular end-systolic volume. Significant increases in time to clinical events and decreased frequency of cardiovascular events were observed at 12 months (hazard ratio=0.12; P=0.003), and mean duration of cardiovascular hospitalizations over 12 months was substantially decreased (0.4 versus 4.5 days; P=0.05) on high-dose treatment versus placebo. There were no untoward safety findings. CONCLUSIONS: CLINICAL TRIAL REGISTRATION: http://www.clinicaltrials.gov. Unique identifier: NCT00454818.
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Authors | Mariell Jessup, Barry Greenberg, Donna Mancini, Thomas Cappola, Daniel F Pauly, Brian Jaski, Alex Yaroshinsky, Krisztina M Zsebo, Howard Dittrich, Roger J Hajjar, Calcium Upregulation by Percutaneous Administration of Gene Therapy in Cardiac Disease (CUPID) Investigators |
Journal | Circulation
(Circulation)
Vol. 124
Issue 3
Pg. 304-13
(Jul 19 2011)
ISSN: 1524-4539 [Electronic] United States |
PMID | 21709064
(Publication Type: Clinical Trial, Phase II, Journal Article, Randomized Controlled Trial, Research Support, Non-U.S. Gov't)
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Chemical References |
- Sarcoplasmic Reticulum Calcium-Transporting ATPases
- Calcium
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Topics |
- Adenoviridae
(genetics)
- Adult
- Aged
- Calcium
(metabolism)
- Disease Progression
- Double-Blind Method
- Exercise Test
- Female
- Genetic Therapy
(adverse effects, methods)
- Heart Diseases
(physiopathology, therapy)
- Heart Failure
(therapy)
- Humans
- Injections, Intra-Arterial
- Male
- Middle Aged
- Oxygen Consumption
(physiology)
- Sarcoplasmic Reticulum Calcium-Transporting ATPases
(genetics)
- Severity of Illness Index
- Treatment Outcome
- Up-Regulation
(physiology)
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