CAPITAL DOREMI 2: Inotrope Versus Placebo Therapy for Cardiogenic Shock
试验速览
- 阶段
- 4 期
- 状态
- 招募中
- 入组人数
- 346
- 试验地点
- 6
- 主要终点
- Primary composite outcome
研究概览
简要总结
The investigators are interested in determining if there is a meaningful benefit from the use of medications purported to increase the pumping function of the heart (i.e. inotropes) among critically ill patients admitted to the Cardiac Intensive Care Unit (CICU). To do this, the investigators will conduct a multi-centre, double blind, randomized control trial with patients who are deemed to require these medications by their treating physician to one of the two most commonly used agents in Canada (Milrinone or Dobutamine) or placebo. Each patient will be closely monitored by their healthcare team. The dose of medication will be adjusted according to each patients' clinical status. After 12 hours, the participants will move to open label treatment and any continued use of inotropes will be at the discretion of their treating physician.
详细描述
Cardiogenic shock (CS) is a state of inadequate end-organ perfusion due to cardiac dysfunction. Acute myocardial infarction (AMI) remains the most prevalent cause of CS, with mortality reaching upwards of 40% despite advances in emergent revascularization and accelerating use of mechanical circulatory support devices. International guidelines support the use of vasopressors and inotropes as a mainstay of medical therapy among this cohort of critically ill patients. Recently, the first head-to-head prospective randomized trial (CAPITAL DOREMI) comparing milrinone and dobutamine in a cohort of CS participants was performed and found no difference between agents.
There is a signal of harm associated with the use of inotropes in both acute, decompensated heart failure and in the longitudinal management of chronic heart failure. Inotrope use has also been associated with longer ICU and in-hospital length of stay, as well as higher in-hospital mortality. A recent network meta-analysis on treatment strategies in CS and found that while milrinone and dobutamine may reduce the risk of mortality compared to placebo, the evidence is of low certainty and the wide confidence intervals do not rule out the possibility of harm.
Despite their frequent use in the management of patients with CS, it remains unknown if inotropes are needed to augment successful initial resuscitation, reduce morbidity and mortality, or if they cause potential harm in this already critically ill patient population.
This study is a multi-centre, double blind, randomized controlled trial designed to examine the efficacy and safety of inotrope therapy against placebo in the initial resuscitation of SCAI class C to D cardiogenic shock. Consecutive patients admitted to an intensive care unit will be identified by the treating medical team as requiring new initiation of inotrope therapy for CS. All decisions to initiate inotrope therapy will be made by the primary care team with no involvement from the research team. The study hypothesis is that inotrope therapy will lead to an overall improvement in the primary outcome as compared to placebo.
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)
盲法说明
Double-blind
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
- •Adult patients ≥ 18 years of age admitted to an intensive care unit
- •SCAI class C or D cardiogenic shock
排除标准
- •Unwilling or unable to obtain informed consent by the participant or substitute decision maker
- •Patients who are currently pregnant or breast-feeding
- •Patients presenting with an out-of-hospital cardiac arrest (OHCA)
- •Administration of milrinone or dobutamine in the 24 hours preceding anticipated randomization
- •Severe obstructive valvular lesions, including aortic stenosis and/or mitral stenosis
- •Dynamic left ventricular outflow tract obstruction
研究组 & 干预措施
Placebo
Participants in the placebo arm will have an intravenous solution of 0.9% NaCl running at a standardized rate, comparable to the infusion rate of the inotrope arm.
干预措施: Normal Saline (Drug)
Inotrope
Participants randomized to receive the inotrope will be initiated on inotrope therapy at starting doses and titrated according to standard clinical care. During reassessment, the treating physicians will make a decision about adjustment of the inotrope dose (increase, maintain or decrease) based on hemodynamics, end-organ perfusion, vasopressor support and clinical exam. Dobutamine doses will be 2.5, 5.0, 7.5, 10 and >10 ug/kg/min and milrinone doses will be 0.125, 0.250, 0.375, 0.5 and >0.5 ug/kg/min. These dose stages are identical to those used in Capital Do-Re-Mi and reflect current standard of care.
干预措施: Dobutamine (Drug)
Inotrope
Participants randomized to receive the inotrope will be initiated on inotrope therapy at starting doses and titrated according to standard clinical care. During reassessment, the treating physicians will make a decision about adjustment of the inotrope dose (increase, maintain or decrease) based on hemodynamics, end-organ perfusion, vasopressor support and clinical exam. Dobutamine doses will be 2.5, 5.0, 7.5, 10 and >10 ug/kg/min and milrinone doses will be 0.125, 0.250, 0.375, 0.5 and >0.5 ug/kg/min. These dose stages are identical to those used in Capital Do-Re-Mi and reflect current standard of care.
干预措施: Milrinone (Drug)
结局指标
主要结局
Primary composite outcome
时间窗: Through duration of hospitalization, up to 12 weeks following admission
The primary outcome will be a composite of: 1. All-cause mortality during the hospitalization 2. Measured within the first 12 hours of starting the study intervention, any of: 1. Sustained hypotension (mean arterial pressure ≤55mmHg) or sustained requirement of high dose vasopressors (norepinephrine \>0.2 mcg/kg/min or norepinephrine 0.2 mcg/kg/min plus any additional agent) with any escalation in dose from time of randomization, for \>/= 60 minutes 2. Lactate greater than 3.5 mmol/L at 6 hours or thereafter 3. Need for mechanical circulatory support device 4. Atrial or ventricular arrhythmia leading to emergent electrical cardioversion 5. Resuscitated cardiac arrest
次要结局
- All-cause in-hospital mortality(Through duration of hospitalization, up to 12 weeks following admission)
- Renal failure requiring new initiation of renal replacement therapy(Through duration of hospitalization, up to 12 weeks following admission)
- Need for cardiac transplant or mechanical circulatory support(Through duration of hospitalization, up to 12 weeks following admission)
- Atrial or ventricular arrhythmia leading to emergent electrical cardioversion(Through duration of hospitalization, up to 12 weeks following admission)
- Resuscitated cardiac arrest(Through duration of hospitalization, up to 12 weeks following admission)
- Non-fatal myocardial infarction(Through duration of hospitalization, up to 12 weeks following admission)
- Stroke or transient ischemic attack(Through duration of hospitalization, up to 12 weeks following admission)