Cyclosporine In Takotsubo Syndrome (CIT) Trial
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 204
- 试验地点
- 41
- 主要终点
- Myocardial damage
研究概览
简要总结
The goal of this clinical trial is to investigate the impact of repetitive acute Cyclosporine A (CsA) bolus therapy in patients suffering from TTS with an elevated risk of impaired outcome. The main question it aims to answer is whether CsA reduces myocardial injury (primary outcome). Participants will receive CsA or placebo at baseline and every 12h in the first 24h after study inclusion. Researchers will compare CsA and the placebo group to see if a) myocardial injury is reduced, and b) ejection fraction is improved compared to baseline, as well as several other secondary endpoints over a one year follow-up.
详细描述
Takotsubo syndrome (TTS) has been suggested to be caused by catecholamine excess with myocardial inflammation-enhanced cardiac injury. Substantial morbidity and mortality have repeatedly been reported, even though reduced ejection fraction frequently recovers spontaneously. So far there is no evidence-based treatment available. In a clinically relevant mouse model of catecholamine-driven TTS, cyclosporine A (CsA) bolus therapy markedly improves outcome, likely mediated via suppression of calcineurin-driven inflammation. The investigators have thus designed a pilot multicentre randomized controlled trial (RCT) to investigate the impact of repetitive CsA bolus therapy vs. placebo in acute TTS patients with an increased risk of intrahospital complications and a 32% estimated 5-year mortality. As primary outcome myocardial damage will be compared between groups via high-sensitive Troponin T plasma area under the curve (AUC). Recovery of cardiac function, the extent of myocardial oedema at 72h, length of hospital-stay, 30-day-, and 1-year composite clinical outcome as well as psychosocial and quality of life self-assessment will be secondary endpoints. The results of this trial may reveal CsA as a first pathophysiology-driven treatment option of TTS and enable a phase III follow-up trial with outcome parameters as primary endpoint.
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
- Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
盲法说明
Participants, investigators, care providers, and outcomes assessors are masked from study arm affiliation.
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
- •Patients aged over 18
- •Enrollment and first IMP administration within 24 hours after cardiac catheterization
- •Regional Wall Motion Abnormality (WMA) consistent with TTS in angiography or echocardiography
- •InterTAK prognostic score- or a GEIST Score ≥ 9 -
- •Written informed consent
排除标准
- •Acute coronary syndrome (ACS) with significant coronary stenosis potentially associated with wall motion abnormalities (WMA) or percutaneous coronary intervention (PCI)
- •Infection (defined as concomitant infection with a positive blood culture at the time of study inclusion)
- •History of hypersensitivity to cyclosporine
- •History of hypersensitivity to egg, peanut or soybean proteins
- •History of chronic renal insufficiency (either creatinin clearance <30 ml/min/1.73m² or current medical care for severe renal insufficiency)
- •History of liver insufficiency
- •Uncontrolled hypertension at the time of screening for study inclusion (systolic blood pressure >180mmHg and/or diastolic blood pressure >110mmHg)
- •Current medication with any compound containing Hypericum perforatum (St. John's worth) or Stiripentol or Aliskiren or Bosentan or Rosuvastatine (Rosuvastatine >5mg within 24h intake<48h before IMP administration)
- •Female patients currently pregnant or women of childbearing age without negative pregnancy test or without effective contraception
- •Any disorder associated with immunological dysfunction ≤6 months prior to presentation (autoimmune disease, known positive serology for HIV or hepatitis)
- •Immunosuppressive, chemotherapeutical, or antibody treatment
- •Participation in other clinical trials except for non interventional trials
研究组 & 干预措施
Placebo
A concealed 0.9% sodium chloride (NaCl) preparation will be applied intravenously at baseline, 12h, and 24h.
干预措施: Placebo (Drug)
CsA
Cyclosporine A will be applied intravenously at baseline, 12h, and 24h.
干预措施: Cyclosporine A (Drug)
结局指标
主要结局
Myocardial damage
时间窗: baseline, hour 3, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30
High-sensitive Troponin T AUC over several time points between CsA and Placebo.
次要结局
- Change in Ejection fraction from baseline(baseline, hour 24, hour 48, hour 72, day 30)
- Fold-change in Troponin plasma concentration(baseline, hour 3, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30)
- Fold-change in creatine kinase plasma concentration(baseline, hour 3, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30)
- Fold-change in NTproBNP plasma concentration(baseline, hour 3, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30)
- Fold-change in interleukin-6 plasma concentration(baseline, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30)
- Fold-change in procalcitonin plasma concentration(baseline, hour 12, hour 24, hour 36, hour 48, hour 60, hour 72, day 30)
- Myocardial edema(hour 72)
- Myocardial inflammation(hour 72)
- Rate of cardiovascular events at day 30(day 30)
- Rate of cardiovascular events at 1 year(1 year)
- Rate of novel disease onset(day 30 and at 1 year)
- Symptom burden at day 30(day 30)
- Symptom burden at 1 year(1 year)
- Depression score at day 30(day 30)
- Depression score at year 1(1 year)
- Anxiety score at day 30(day 30)
- Anxiety score at year 1(year 1)
- PTSD score at 30 days(day 30)
- PTSD score at 1 year(year 1)
- Length of intermediate care or intensive care unit stay(day 30)
- Length of hospital stay(day 30)
研究者
Norbert Frey, MD
Professor Dr. Norbert Frey, MD
University Hospital Heidelberg