NCT03146741已完成1 期
Open-Labeled Trial Of Zepatier For Treatment Of Hepatitis C-Negative Patients Who Receive Heart Transplants From Hepatitis C-Positive Donors
适应症
干预措施
相关药物
试验速览
- 阶段
- 1 期
- 状态
- 已完成
- 入组人数
- 20
- 试验地点
- 1
- 主要终点
- Number of Participants With Post-treatment Sustained Virologic Response (SVR)
研究概览
简要总结
This study is being conducted to determine safety and effectiveness of transplanting hearts from Hepatitis C-positive donors into Hepatitis C-negative patients on the heart transplant waitlist, who will then be treated with Zepatier after transplantation.
详细描述
Open-labelled pilot clinical trial of Zepatier (MK-5172 and MK-8742/Grazoprevir + Elbasvir) in at least 20 HCV-negative subjects receiving a heart transplant from a HCV-positive donor. Eligible subjects will receive a heart transplant from a deceased-donor with genotype 1 or 4 HCV, and then will receive 12 weeks of Zepatier after heart transplantation when infection with HCV is confirmed in these heart transplant recipients. Treatment will be complete after 12 weeks.
研究设计
- 研究类型
- Interventional
- 分配方式
- Na
- 干预模型
- Single Group
- 主要目的
- Treatment
- 盲法
- None
入排标准
- 年龄范围
- 18 Years 至 65 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •New York Heart Association (NYHA) Class III or IV CHF refractory to maximal medical therapy (ACE inhibitor, B-blocker, digoxin and diuretics, resynchronization therapy or Implantable Cardioverter Defibrillator when applicable) and/or conventional surgery.
- •Inoperable coronary artery disease with intractable anginal symptoms
- •Malignant ventricular arrhythmias unresponsive to medical or surgical therapy
- •18-65 years of age
- •Obtained agreement for participation from the transplant cardiology team
- •No evident contraindication to liver transplantation other than the underlying cardiac disorder
- •Able to travel to the University of Pennsylvania for routine post-transplant visits and study visits for a minimum of 6 months after transplantation
- •No active illicit substance abuse
- •Women must agree to use birth control in accordance with Mycophenolate Risk Evaluation and Mitigation Strategy (REMS) following transplant due to the increased risk of birth defects and/or miscarriage
- •Both men and women must agree to use at least one barrier method of birth control or remain abstinent following transplant due to risk of HCV transmission
- •Inclusion criteria for treatment (not for entry as study patient) will include any detectable HCV RNA by week 4 post-heart transplantation
- •Able to provide informed consent
排除标准
- •Hepatocellular carcinoma
- •HIV positive
- •HCV antibody positive and/or RNA positive
- •Hepatitis B surface antigen, core antibody, and/or DNA positive
- •Any other chronic liver disease (excluding non-alcoholic fatty liver disease (NAFLD) with abnormal liver enzymes
- •Persistently elevated liver transaminases
- •Congenital heart disease
- •Fibrosis by liver biopsy or total bilirubin > 2.5 with associated evidence of synthetic dysfunction.
- •Pregnant or nursing (lactating) women
- •Known allergy or intolerance to tacrolimus that would require post-transplant administration of cyclosporine, rather than tacrolimus given the drug-drug interaction between cyclosporine and ZEPATIER
- •Waitlisted for a multi-organ transplant
- •Evidence of end organ damage due to diabetes (e.g. retinopathy, nephropathy, ulcerations) and /or brittle diabetes mellitus (e.g. history of diabetic ketoacidosis) and/or uncontrolled diabetes as evidence by a HgbA1C of 7.5-8.
- •Chronic bronchitis, chronic obstructive pulmonary disease, inability to stop smoking.
- •Hematologic: Significant coagulation abnormalities, bleeding diatheses.
- •Psychosocial: Profound neurocognitive impairment with absence of social support.
- •Active mental illness or psychosocial instability
- •Inadequate insurance or financial support for post-transplant care.
- •Evidence of drug, tobacco or alcohol abuse within the past six months and completion of recommended therapy/services or meets satisfied parameters as indicated by social work staff and/or consult team.
- •History of chronic non-compliance.
- •Amyloidosis (restricted to cardiac only, without evidence of extra cardiac involvement)
- •Active peptic ulcer disease.
- •Severe malnutrition.
- •Major chronic disabling illness (e.g. lupus, severe arthritis, neurologic diseases, previous stroke with profound residual).
- •Pulmonary infarction within the past 6 weeks
- •Severe pulmonary hypertension as evidenced by a fixed pulmonary vascular resistance of greater than 4 Wood units on appropriate medical therapy.
- •Patient refusal to receive blood products or transfusions during heart transplant surgery.
- •Severe chronic obstructive pulmonary disease
- •Current clinical sepsis.
- •Symptomatic or severe vascular disease.
- •Chronic Kidney Disease Stage IV, Glomerular Filtration Rate < 30
- •History of Mantle radiation.
- •Asymptomatic renal cell carcinoma <1 year from curative treatment.
- •Symptomatic renal cell carcinoma <5 years from curative treatment.
- •Prostate cancer <2 years from curative treatment.
- •Uterine or cervical cancer <2 years from curative treatment.
- •Any other cancer other than the above including malignant melanoma, < 5 years from treatment apart from other skin malignancies.
- •Donor Organ Selection Criteria:
- •General criteria (although there can be exceptions on a case-by-case basis)
- •Detectable HCV RNA
- •Genotype 1 or 4 HCV
- •Age <=55 years
- •No history of coronary artery disease
- •No congenital heart disease except a repaired atrial septal defect (ASD) provided the patient has normal right ventricular function
- •No history of arrhythmia (atrial fibrilation, atrial flutter or VT) except during resuscitation from fatal event.
- •No evidence of cirrhosis
- •Echocardiographic criteria:
- •Left ventricular ejection fraction (LVEF) >=50%
- •Normal right ventricular function
- •No left ventricular hypertrophy (LVH) - septal wall thickness <1 cm
- •No left ventricular hypertrophy (LVH)- posterior wall thickness <1 cm
- 另有 7 项未显示
研究组 & 干预措施
Zepatier (grazoprevir 100mg and elbasvir 50 mg)
Experimental
干预措施: Zepatier (Drug)
结局指标
主要结局
Number of Participants With Post-treatment Sustained Virologic Response (SVR)
时间窗: Baseline to 24 weeks
The primary analysis will be based on a calculation of SVR rates (number of subjects with SVR; negative HCV RNA after completing Zepatier therapy) / (number of subjects treated with Zepatier post-heart transplantation)
Number of Severe Adverse Events (SAE) Attributable to HCV Therapy Post-heart Transplant
时间窗: Baseline to 52 weeks
次要结局
未报告次要终点
研究者
研究点 (1)
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