PMID- 29763816
OWN - NLM
STAT- MEDLINE
DCOM- 20190418
LR  - 20190418
IS  - 1097-6744 (Electronic)
IS  - 0002-8703 (Linking)
VI  - 201
DP  - 2018 Jul
TI  - Design of a Phase 3 trial of intracoronary administration of human adenovirus 5
      encoding human adenylyl cyclase type 6 (RT-100) gene transfer in patients with
      heart failure with reduced left ventricular ejection fraction: The FLOURISH
      Clinical Trial.
PG  - 111-116
LID - S0002-8703(18)30112-1 [pii]
LID - 10.1016/j.ahj.2018.04.005 [doi]
AB  - The prognosis of patients with HFrEF remains poor despite the use of current
      medical and device therapies. Preclinical studies of HFrEF using IC delivery of
      RT-100, a replication deficient, E1/E3-deleted human adenovirus 5 encoding human 
      AC6 was associated with favorable effects on LV function and remodeling. A recent
      multicenter, double-blind, placebo-controlled, phase 2 study demonstrated the
      safety of IC delivery of RT-100 in HFrEF patients and potential efficacy at the
      higher doses. This phase 2 dose finding study, which included doses not expected 
      to be effective, identified a potential reduction in congestive heart failure
      admissions in the AC6-treated group one year after randomization. The FLOURISH
      study is designed to investigate the prospect of reduction of heart failure
      hospitalization and other clinical adverse events and improvement in EF. The
      FLOURISH study is a double-blind, placebo-controlled, multicenter Phase 3
      clinical trial that will randomize 536 patients to a one-time IC administration
      of RT-100 (10(12) vp) or placebo in a 1:1 ratio. Subjects will be 18-80 years of 
      age, on optimal standard of care HF therapy with LVEF >/=10% and </=35% by
      echocardiogram, and will undergo IC administration of RT-100 vs. placebo on Day
      1. Follow-up study visits will be performed at Weeks 1 and 4, and Months 3, 6,
      and 12. Patients will be followed for an additional 36 months for safety
      assessments with telephone contact at Months 24, 36, and 48. The primary
      objective is to determine the efficacy of IC RT-100 vs. placebo in reducing the
      event rate of all (first and repeat) HF hospitalizations occurring from baseline 
      to 12 months. The secondary objectives are to determine the efficacy of IC RT-100
      on CV death, all cause death, and all HF events and in improving NYHA functional 
      classification. Exploratory endpoints will include echocardiographic parameters
      of left ventricular systolic and diastolic function, HF symptoms and physical
      limitations, 6-minute walking distance, Borg dyspnea score, and NT-proBNP levels.
      The FLOURISH study, which received fast track designation from the Food and Drug 
      Administration in December 2017, will further investigate the role of a one-time 
      intracoronary injection of RT-100 in reducing HF hospitalizations and will serve 
      as a registration trial (potentially pivotal investigation) for RT-100 as a
      treatment for HFrEF.
CI  - Copyright (c) 2018. Published by Elsevier Inc.
FAU - Penny, William F
AU  - Penny WF
AD  - Veterans Affairs San Diego Healthcare System and Department of Medicine,
      University of California, San Diego, CA. Electronic address: wpenny@ucsd.edu.
FAU - Henry, Timothy D
AU  - Henry TD
AD  - Cedars Sinai Heart Institute, Los Angeles, CA.
FAU - Watkins, Matthew W
AU  - Watkins MW
AD  - Department of Medicine, University of Vermont Medical Center, Burlington, VT.
FAU - Patel, Amit N
AU  - Patel AN
AD  - Department of Medicine, University of Miami, Miami, FL.
FAU - Hammond, H Kirk
AU  - Hammond HK
AD  - Veterans Affairs San Diego Healthcare System and Department of Medicine,
      University of California, San Diego, CA.
LA  - eng
PT  - Journal Article
PT  - Review
DEP - 20180406
PL  - United States
TA  - Am Heart J
JT  - American heart journal
JID - 0370465
RN  - EC 4.6.1.1 (Adenylyl Cyclases)
RN  - EC 4.6.1.1 (adenylyl cyclase 6)
SB  - AIM
SB  - IM
MH  - Adenoviruses, Human
MH  - Adenylyl Cyclases/*administration & dosage
MH  - Clinical Trials, Phase III as Topic/*methods
MH  - Coronary Vessels
MH  - *Gene Transfer Techniques
MH  - Genetic Therapy/*methods
MH  - Heart Failure/physiopathology/*therapy
MH  - Humans
MH  - Injections, Intra-Arterial
MH  - Randomized Controlled Trials as Topic/*methods
MH  - Stroke Volume/*physiology
MH  - Ventricular Function, Left/physiology
EDAT- 2018/05/16 06:00
MHDA- 2019/04/19 06:00
CRDT- 2018/05/16 06:00
PHST- 2017/11/16 00:00 [received]
PHST- 2018/04/02 00:00 [accepted]
PHST- 2018/05/16 06:00 [pubmed]
PHST- 2019/04/19 06:00 [medline]
PHST- 2018/05/16 06:00 [entrez]
AID - S0002-8703(18)30112-1 [pii]
AID - 10.1016/j.ahj.2018.04.005 [doi]
PST - ppublish
SO  - Am Heart J. 2018 Jul;201:111-116. doi: 10.1016/j.ahj.2018.04.005. Epub 2018 Apr
      6.