A Double-blind, Randomized, Placebo-controlled, Multicenter Study to Assess the Efficacy and Safety of Omecamtiv Mecarbil on Mortality and Morbidity in Subjects With Chronic Heart Failure With Reduced Ejection Fraction (GALACTIC-HF)
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 发起方
- 入组人数
- 8,256
- 试验地点
- 1
- 主要终点
- Time to Cardiovascular Death or First Heart Failure Event
研究概览
简要总结
The purpose of this study is to determine if treatment with omecamtiv mecarbil when added to standard of care is well tolerated and superior to placebo in reducing the risk of cardiovascular death or heart failure events in adults with chronic heart failure with reduced ejection fraction (HFrEF).
详细描述
This study was conducted by Amgen as the IND holder, with Cytokinetics as a collaborator. Due to the termination of the collaboration agreement between Amgen and Cytokinetics in May 2021 and subsequent transfer of the omecamtiv mecarbil IND from Amgen to Cytokinetics, Cytokinetics is now listed as the sponsor.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Parallel
- 主要目的
- Treatment
- 盲法
- Triple (Participant, Care Provider, Investigator)
入排标准
- 年龄范围
- 18 Years 至 85 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Subject has provided informed consent
- •Male or female, ≥ 18 to ≤ 85 years
- •History of chronic heart failure (HF), defined as requiring treatment for HF for a minimum of 30 days before randomization
- •Left ventricle ejection fraction (LVEF) ≤ 35%, per subjects most recent medical record, within 12 months prior to screening.
- •New York Heart Association (NYHA) class II to IV at most recent screening assessment.
- •Managed with HF standard of care (SoC) therapies consistent with regional clinical practice guidelines according to investigator judgment of subject's clinical status
- •Current hospitalization with primary reason of HF OR one of the following events within 1 year of screening: hospitalization with primary reason of HF; urgent visit to emergency department (ED) with primary reason of HF.
- •Elevated B-type natriuretic peptide (BNP) or n-terminal-prohormone brain natriuretic peptide (NT-proBNP)
- •Other Inclusion Criteria May apply
排除标准
- •Currently receiving treatment in another investigational device or drug study, or < 30 days since ending treatment on another investigational device or drug study(ies). Other investigational procedures while participating in this study are excluded.
- •Malignancy within 5 years prior to randomization with the following exceptions: localized basal or squamous cell carcinoma of the skin, cervical intraepithelial neoplasia, stage 1 prostate carcinoma, breast ductal carcinoma in situ.
- •Subject has known sensitivity to any of the products or components to be administered during testing
- •Other Exclusion Criteria May apply
研究组 & 干预措施
Omecamtiv Mecarbil
Participants received oral omecamtiv mecarbil (OM) twice daily in addition to standard heart failure therapy. The starting dose of OM was 25 mg; At week 4, participants with week 2 OM predose plasma concentrations < 200 ng/mL had their dose increased to 50 mg BID; participants with week 2 predose plasma concentrations ≥ 200 and < 300 ng/mL had their dose increased to 37.5 mg BID and participants with week 2 predose plasma concentrations ≥ 300 ng/mL and < 1000 ng/mL maintained a 25 mg BID dosing regimen.
干预措施: Omecamtiv Mecarbil (Drug)
Omecamtiv Mecarbil
Participants received oral omecamtiv mecarbil (OM) twice daily in addition to standard heart failure therapy. The starting dose of OM was 25 mg; At week 4, participants with week 2 OM predose plasma concentrations < 200 ng/mL had their dose increased to 50 mg BID; participants with week 2 predose plasma concentrations ≥ 200 and < 300 ng/mL had their dose increased to 37.5 mg BID and participants with week 2 predose plasma concentrations ≥ 300 ng/mL and < 1000 ng/mL maintained a 25 mg BID dosing regimen.
干预措施: Standard of Care (Drug)
Placebo
Participants received matching placebo tablets twice a day in addition to standard heart failure therapy.
干预措施: Placebo (Drug)
Placebo
Participants received matching placebo tablets twice a day in addition to standard heart failure therapy.
干预措施: Standard of Care (Drug)
结局指标
主要结局
Time to Cardiovascular Death or First Heart Failure Event
时间窗: From randomization to up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months.
The primary outcome was a composite of a heart-failure (HF) event or cardiovascular (CV) death, whichever occurred first, in a time-to-event analysis. A heart-failure event was defined as an urgent clinic visit, emergency department visit, or hospitalization for subjectively and objectively worsening heart failure leading to treatment intensification beyond a change in oral diuretic therapy. All deaths and HF events were adjudicated by an independent external clinical events committee (CEC) at the Duke Clinical Research Institute, using standardized definitions based on the recent American College of Cardiology/American Heart Association (ACC/AHA) standards for endpoint definitions in cardiovascular clinical trials. Time to cardiovascular death or first HF event was analyzed using Kaplan-Meier (KM) methods. Since the median was not calculated, the percentage of participants with a positively adjudicated event during the study is reported.
次要结局
- Time to Cardiovascular Death(From randomization to up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months.)
- Change From Baseline in Kansas City Cardiomyopathy Questionnaire Total Symptom Score (KCCQ TSS) at Week 24(Baseline and Week 24)
- Time to First Heart Failure Hospitalization(From randomization to up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months.)
- Time to All-cause Death(From randomization up to earliest of last confirmed survival status date or analysis cut-off date (07 August 2020); the overall median duration of follow-up was 21.8 months up to a maximum of 42 months.)