Double-blind, placebo-controlled study of the efficacy of flosequinan in patients with chronic heart failure. Principal Investigators of the REFLECT Study - PubMed (original) (raw)
Clinical Trial
Double-blind, placebo-controlled study of the efficacy of flosequinan in patients with chronic heart failure. Principal Investigators of the REFLECT Study
M Packer et al. J Am Coll Cardiol. 1993 Jul.
Free article
Abstract
Objectives: The aim of this study was to assess the efficacy of flosequinan in chronic heart failure.
Background: Flosequinan is a new vasodilator drug that acts by interfering with the inositol-triphosphate/protein kinase C pathway, an important mechanism of vasoconstriction. The drug dilates both peripheral arteries and veins, is orally active and has a long duration of action that permits once-daily dosing. Previous studies have shown that flosequinan produces sustained hemodynamic benefits in heart failure, but large scale studies evaluating its clinical efficacy have not been reported.
Methods: One hundred ninety-three patients with chronic heart failure (New York Heart Association functional class II or III and left ventricular ejection fraction < 40%) receiving digoxin and diuretic drugs were randomly assigned (double-blind) to the addition of flosequinan (100 mg once daily, n = 93) or placebo (n = 100) for 3 months. The clinical status and exercise tolerance of each patient was evaluated at the start of the study and every 2 to 4 weeks during the trial while background therapy remained constant.
Results: After 12 weeks, maximal treadmill exercise time increased by 96 s in the flosequinan group but by only 47 s in the placebo group (p = 0.022 for the difference between groups). Maximal oxygen consumption increased by 1.7 ml/kg per min in the flosequinan group (n = 17) but by only 0.6 ml/kg per min in the placebo group (n = 23), p = 0.05 between the groups. Symptomatically, 55% of patients receiving flosequinan but only 36% of patients receiving placebo benefited from treatment (p = 0.018). In addition, fewer patients treated with flosequinan had sufficiently severe worsening of heart failure to require a change in medication or withdrawal from the study (p = 0.07). By intention to treat, seven patients in the flosequinan group and two patients in the placebo group died.
Conclusions: These findings indicate that flosequinan is an effective drug for patients with chronic heart failure who remain symptomatic despite treatment with digoxin and diuretic drugs. The effect of the drug on survival remains to be determined.
Similar articles
- Can further benefit be achieved by adding flosequinan to patients with congestive heart failure who remain symptomatic on diuretic, digoxin, and an angiotensin converting enzyme inhibitor? Results of the flosequinan-ACE inhibitor trial (FACET).
Massie BM, Berk MR, Brozena SC, Elkayam U, Plehn JF, Kukin ML, Packer M, Murphy BE, Neuberg GW, Steingart RM, et al. Massie BM, et al. Circulation. 1993 Aug;88(2):492-501. doi: 10.1161/01.cir.88.2.492. Circulation. 1993. PMID: 8339411 Clinical Trial. - Flosequinan in chronic heart failure: how is exercise capacity improved?
Banning AP, Ramsey MW, Jones EA, Evans W, Carolan G, Jones CH, Henderson AH. Banning AP, et al. Eur J Clin Pharmacol. 1996;51(2):133-8. doi: 10.1007/s002280050173. Eur J Clin Pharmacol. 1996. PMID: 8911877 Clinical Trial. - Effect of flosequinan on exercise capacity and cardiac function in patients with chronic mild heart failure: a double-blind placebo-controlled study.
Hori M, Sato H, Ozaki H, Inoue M, Naka M, Fukunami M, Fukushima M, Kunisada K. Hori M, et al. Heart Vessels. 1992;7(3):133-40. doi: 10.1007/BF01744866. Heart Vessels. 1992. PMID: 1500398 Clinical Trial. - Long-Term Effects of Flosequinan on the Morbidity and Mortality of Patients With Severe Chronic Heart Failure: Primary Results of the PROFILE Trial After 24 Years.
Packer M, Pitt B, Rouleau JL, Swedberg K, DeMets DL, Fisher L. Packer M, et al. JACC Heart Fail. 2017 Jun;5(6):399-407. doi: 10.1016/j.jchf.2017.03.003. Epub 2017 May 10. JACC Heart Fail. 2017. PMID: 28501522 Clinical Trial. - Flosequinan for chronic heart failure?
[No authors listed] [No authors listed] Drug Ther Bull. 1993 Jun 7;31(12):47-8. Drug Ther Bull. 1993. PMID: 8344139 Review. No abstract available.
Cited by
- An Update on Protein Kinases as Therapeutic Targets-Part I: Protein Kinase C Activation and Its Role in Cancer and Cardiovascular Diseases.
Silnitsky S, Rubin SJS, Zerihun M, Qvit N. Silnitsky S, et al. Int J Mol Sci. 2023 Dec 18;24(24):17600. doi: 10.3390/ijms242417600. Int J Mol Sci. 2023. PMID: 38139428 Free PMC article. Review. - Lack of durable natriuresis and objective decongestion following SGLT2 inhibition in randomized controlled trials of patients with heart failure.
Packer M. Packer M. Cardiovasc Diabetol. 2023 Aug 2;22(1):197. doi: 10.1186/s12933-023-01946-w. Cardiovasc Diabetol. 2023. PMID: 37533009 Free PMC article. Review. - Role and Mechanism of PKC-δ for Cardiovascular Disease: Current Status and Perspective.
Miao LN, Pan D, Shi J, Du JP, Chen PF, Gao J, Yu Y, Shi DZ, Guo M. Miao LN, et al. Front Cardiovasc Med. 2022 Feb 15;9:816369. doi: 10.3389/fcvm.2022.816369. eCollection 2022. Front Cardiovasc Med. 2022. PMID: 35242825 Free PMC article. Review. - Diacylglycerol-evoked activation of PKC and PKD isoforms in regulation of glucose and lipid metabolism: a review.
Kolczynska K, Loza-Valdes A, Hawro I, Sumara G. Kolczynska K, et al. Lipids Health Dis. 2020 May 28;19(1):113. doi: 10.1186/s12944-020-01286-8. Lipids Health Dis. 2020. PMID: 32466765 Free PMC article. Review. - Phase II Trials in Drug Development and Adaptive Trial Design.
Van Norman GA. Van Norman GA. JACC Basic Transl Sci. 2019 Jun 24;4(3):428-437. doi: 10.1016/j.jacbts.2019.02.005. eCollection 2019 Jun. JACC Basic Transl Sci. 2019. PMID: 31312766 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical