Investigator Sponsored Research Proposal : Efficacy and Safety of Combination Ambrisentan and TadaLafil in PATiEnts With PortoPulmonary Hypertension (ESCALATE-PPH)
试验速览
- 阶段
- 4 期
- 状态
- 撤回
- 试验地点
- 1
- 主要终点
- Reduction in mPAP to 35mmHg
研究概览
简要总结
The purpose of this study is to evaluate the efficacy and safety of the combination of ambrisentan and tadalafil in reducing mPAP to below 35mmHg in patients with moderate to severe Portopulmonary Hypertension (POPH) as a means to candidacy for liver transplantation.
详细描述
The outcome of liver transplantation (LT) in the presence of moderate to severe POPH is significantly poor with a 50% reported mortality rate in LT recipients having a mean pulmonary artery pressure (mPAP) >35 mmHg and 100% when the mPAP is greater than 50 mmHg; therefore, making moderate to severe POPH a contraindication to liver transplants. Those recipients with significant pulmonary artery pressure (PAP) may be denied the opportunity for transplant unless the mPAP is brought below 35 mmHg with medical treatment. This study will test the efficacy & safety of the combination of using ambrisentan and tadalfil in reducing the Pulmonary Arterial Pressure to below 35 mmHg in patients with moderate to severe POPH as a means to candidacy for liver transplantation.
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 —（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Child-Pugh Class Class A & B Cirrhosis
- •mPAP ≥35mmHg
- •Pulmonary Capillary Wedge Pressure (PWCP) <15mmHg on Right Heart Catheterization's (RHCs)
- •mPAP > 50mmHg will be considered eligible unless they are World Health Organization (WHO) Functional Class IV
排除标准
- •End stage renal disease on hemodialysis (ESRD on HD)
- •Renal dysfunction and GFR < 30
- •AST, ALT > 5 times the upper limit of normal
- •Total bilirubin ≥ 6.0
- •Initially, Child-Pugh Class C patients will be excluded; however, after the first 5 patients are included, if there is no signal of worsening liver function, the protocol may be amended to include patients with Class C cirrhosis.
研究组 & 干预措施
Combination Therapy
Qualifying participants will begin combination therapy with ambrisentan pill 5 mg daily and tadalafil pill 20 mg. After one week of therapy, patients will increase tadalafil pill to 40 mg daily and continue ambrisentan pill 5 mg daily. On day 15, patients will increase ambrisentan pill to 10 mg daily and continue at 40 mg of tadalafil pill daily.
干预措施: Ambrisentan Pill (Drug)
Combination Therapy
Qualifying participants will begin combination therapy with ambrisentan pill 5 mg daily and tadalafil pill 20 mg. After one week of therapy, patients will increase tadalafil pill to 40 mg daily and continue ambrisentan pill 5 mg daily. On day 15, patients will increase ambrisentan pill to 10 mg daily and continue at 40 mg of tadalafil pill daily.
干预措施: Tadalafil Pill (Drug)
结局指标
主要结局
Reduction in mPAP to 35mmHg
时间窗: 2 months post initiation of therapy
A Right Heart Catheterization will be performed in order to see if there's a reduction in mPAP to less than 35mmHg from baseline
次要结局
- Post-Transplant Survival Outcome: Alive or Dead at 30 days(Post-op Day 1 and 30)
- Liver Function test measured by AST (iu/L)(baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant)
- Right Ventricular (RV) Function in centimeters(Baseline, 1-month, 6-month and 12 months post therapy and 1-month post transplant)
- Biomarker of Right ventricular failure(baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant)
- New York Heart Association Functional class(baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant)
- Liver Function test measured by Bilirubin (mg/dL)(baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant)
- Blood Pressure(2 months post therapy)
- mPAP Reduction(2 months post initiation of therapy)
- Kidney function evaluation through measurement of Creatinine levels (mg/dL)(baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant)
- Liver Function test measured by ALT (iu/L)(baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant)
- Liver Function test measured by INR(baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant)
- Right Ventricular (RV) Size in centimeters(Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant)
- Right Ventricular (RV) Qualitative Systolic Function: assessment that is categorized as normal, mildly depressed, moderately depressed or severely depressed(Baseline, 1-month, 6-month and 12 months post therapy, 1 month post transplant)
- Change in 6 Minute Walk Distance(baseline, 1 month, 2 month, 3 month, 6 month, 9 month, 12 months/end of treatment, 1 month post transplant)