NCT01848639已完成3 期
ALdosterone Antagonist Chronic HEModialysis Interventional Survival Trial (ALCHEMIST), Phase III b
适应症
干预措施
相关药物
试验速览
- 阶段
- 3 期
- 状态
- 已完成
- 入组人数
- 823
- 试验地点
- 70
- 主要终点
- The time to onset of the first incident :non-fatal MI or acute coronary syndrome or hospitalization for heart failure or nonfatal stroke or cardiovascular (CV) death
研究概览
简要总结
This study is designed to etablish the effects of spironolactone in comparison to placebo on the composite endpoint of nonfatal Myocardial Infarction (MI) and acute coronary syndrome, hospitalization for heart failure, nonfatal stroke or cardiovascular-induced death. The primary endpoint will be the time to onset of the first incident.
详细描述
- During a run-in period : Spironolactone will be initially administered per os at a 25 mg dose per two days in practice after the session, three times per week
- Patients will be randomized (spironolactone vs. placebo) and titrated over one month to a maximum single dose of 25 mg/d
- However if kalemia is greater than or equal to 5.5 mmol / l twice on this run-in period or on the day of randomization, patient won't be randomized.
- A pre-specified algorithm for the management of the risk of incident hyperkalemia will be followed, including dose adjustment, temporary cessation of study treatment, in addition to usual dietary measures and the use of chelating resins and low-potassium dialysis baths
- Patients will be followed for a mean of 2 years.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Written informed consent.
- •Adult men and women on HD for at least 45 days for ESRD regardless of the etiology including diabetes, with at least 3 HD sessions per week
- •Presenting at least one of the follow comorbidities, cardiovascular abnormalities or CV risk factors:
- •Left ventricular hypertrophy defined by left ventricular mass > 130 g/m2 in men and 100 g/m2 in women (echocardiography)
- •OR Cornell (RaVL + SV3) >28 mm in men, > 20 mm in women(ECG)
- •OR left ventricular ejection fraction < 40%
- •OR large QRS > 0.14 sec
- •OR Left bundle branch block (ECG) measured during the twelve months preceding inclusion; diabetes;
- •OR history of cardiovascular disease: coronary artery disease, symptomatic lower limb peripheral arterial disease, carotid or renal artery stenosis > 50%, stroke, hospitalization for heart failure, permanent atrial fibrillation (AF), oral anticoagulant treatment for AF, valvular heart prosthesis,
- •OR CRP > 5 mg/l for 3 months without infectious or neoplastic disease documented in progress
排除标准
- •history of hypersensitivity to spironolactone or galactose intolerance
- •the Lapp lactase deficiency or malabsorption of glucose or galactose
- •hyperkalemia > 5.5 mmol/l during the two weeks prior to enrolment
- •history of unscheduled hemodialysis for hyperkalemia during the last six months
- •hospitalization for hyperkalemia during the last six months
- •patients with imperative indication of a combination of ACEI and sartan or renin inhibitor (each being authorized separately), NSAIDS, Cox-2 inhibitors
- •kidney transplant scheduled within the year
- •symptomatic interdialytic hypotension
- •acute systemic disease
- •uncompensated hypothyroidism
- •acute hyperthyroidism
- •any prior or concomitant clinical condition compromising the inclusion, in the discretion of the investigator
- •cardiac transplant
- •severe uncontrolled arrhythmia
- •stroke within 3 months prior to enrolment
- •acute coronary syndrome in the previous month inclusion
- •recent (1 month) or planned coronary revascularization by angioplasty
- •recent (3 months) or planned cardiovascular surgery (excluding HD vascular access)
- •non menopausal women or without effective contraceptive methods
- •pregnancy, breastfeeding or planning a pregnancy within 2 years
- •non compliance
- •protected adult
- •SBP > 200 mmHg and/or DBP > 110 mmHg
- •Concomitant treatment can not be stopped by another potassium-sparing diuretic, a potassium supplements, AINS or Cox 2 inhibitors
研究组 & 干预措施
Spironolactone
Active Comparator
After a month in run-in period under 25 mg per 2 days of spironolactone administered per os in practice after dialysis session three times a week, patients will be randomized to spironolactone. The dose should be increased to 25 mg once daily and could be adjusted in using an algorithm used in the EPHESUS and EMPHASIS-HF trials.
干预措施: Spironolactone (Drug)
Placebo
Placebo Comparator
After a month in run-in period under 25 mg per 2 days of spironolactone administered per os in practice after dialysis session three times a week, patients will be randomized to placebo. The dose should be increased to 25 mg once daily and could be adjusted in using an algorithm used in the EPHESUS and EMPHASIS-HF trials.
干预措施: Placebo (Drug)
结局指标
主要结局
The time to onset of the first incident :non-fatal MI or acute coronary syndrome or hospitalization for heart failure or nonfatal stroke or cardiovascular (CV) death
时间窗: 25 months
次要结局
- Determine the effects of spironolactone compared to placebo on the composite winratio endpoint(24 months)
- non-cardiovascular mortality rate(24 months)
- cumulative accident rates forming the primary endpoint(24 months)
- The time of survival without a major CV event (non fatal MI, acute coronary syndrome, hospitalization for heart failure, non-fatal stroke, cardiac arrest resuscitation)(24 months)
- Incidence of procedures related to stenosis or vascular access thrombosis for hemodialysis (HD)(24 months)
- Incidence of coronary or peripheral revascularizations (including lower limb amputations)(24 months)
- Blood pressure (systolic and diastolic pressure)(24 months)
- Blood pressure's variability inter visit (systolic and diastolic pressure)(24 months)
- The occurrence of atrial fibrillation(24 months)
- Incidence of hyperkalemia> 6 mmol/l(24 months)
- Estimation of the effect of treatment on quality of life.(24 months)
研究者
研究点 (70)
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