CombinatiON Up-FRON t Therapy for PAH - A Phase 4, Randomized, Multicenter Study of Inhaled Treprostinil in Treatment naïve Pulmonary Arterial Hypertension Patients Starting on Tadalafil
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 21
- 试验地点
- 2
- 主要终点
- Change in Right Ventricular Ejection Fraction
研究概览
简要总结
The Study Hypothesis:
Aggressive, upfront, dual therapy for treatment-naïve NYHA I/II/III PAH is superior to a traditional "step-up" approach.
The study will evaluate:
- Impact of dual, upfront, therapy on cardiovascular parameters in PAH as gauged by cardiac magnetic resonance imaging (cMRI) at 24 weeks and event free survival at outcome at 48 weeks.
- Value of novel biomarkers (NT-pro BNP, Mts1/S100A4, and insulin resistance) and cutting-edge imaging technologies (cardiac MRI) as newer endpoints for clinical trials in PAH.
- Utility of longer clinical trial design with the use of combined clinical events as time to clinical worsening surrogate
详细描述
This is a 48 week interventional study evaluating the effect of Dual therapy ( Treprostinil inhalations and Tadalafil) versus Mono therapy (Tadalafil). The impact of the therapy on cardiovascular parameters in PAH measured at 24 weeks and event free survival outcome at 48 weeks.
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 69 Years（Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- 未提供
排除标准
- •Exclusion criteria:
- •Group II - V pulmonary hypertension.
- •PAH with unrepaired congenital heart defect.
- •Current or prior PAH treatments within the last 6-12 months including experimental PAH therapies (including but not limited to tyrosine kinase inhibitors, rho-kinase inhibitors, phosphodiesterase inhibitors, prostacycline, or cGMP modulators).
- •TLC < 60% predicted; if TLC b/w 60 and 70% predicted, high resolution computed tomography must be available to exclude significant interstitial lung disease.
- •FEV1 / FVC < 70% predicted and FEV1 < 60% predicted
- •Significant left-sided heart disease (based on pre-trial Echocardiogram):
- •Significant aortic or mitral valve disease
- •Diastolic dysfunction ; Grade II C.LV systolic function < 45%
- •d. Pericardial constriction e. Restrictive cardiomyopathy f. Significant coronary disease with demonstrable ischemia
- •Chronic renal insufficiency defined as an estimated creatinine clearance < 30 ml/min (by MDRD equation)
- •Current atrial arrhythmias
- •Uncontrolled systemic hypertension: SBP > 160 mm or DBP > 100mm
- •Severe hypotension: SBP < 80 mmHg.
- •Pregnant or breast-feeding
- •Psychiatric, addictive, or other disorder that compromises patient's ability to provide informed consent, follow study protocol, and adhere to treatment instructions
- •Co-morbid conditions that would impair a patient's exercise performance and ability to assess WHO functional class, including but not limited to chronic low-back pain or peripheral musculoskeletal problems.
- •Contraindications for magnetic resonance imaging, including significant claustrophobia, implanted metallic objects, or others as per Appendix X).
- •Known allergy to treprostinil or tadalafil.
- •Active oral nitrate use.
- •Diabetes mellitus.
- •Planned initiation of cardiac or pulmonary rehabilitation during period of study.
研究组 & 干预措施
tadalafil alone
tadalafil 40mg QD(Tadalafil 20 mg QD PO increasing to 40 mg QD as tolerated).
干预措施: tadalafil (Drug)
tadalafil and treprostinil inhalations
Treprostinil inhalation QID starting at 3 breaths per inhalation & gradually increasing to 9 breaths.Each breath provides approximately 6 mcg of treprostinil.Tadalafil 20 mg QD PO increasing to 40 mg QD as tolerated.
干预措施: treprostinil inhalations (Drug)
tadalafil and treprostinil inhalations
Treprostinil inhalation QID starting at 3 breaths per inhalation & gradually increasing to 9 breaths.Each breath provides approximately 6 mcg of treprostinil.Tadalafil 20 mg QD PO increasing to 40 mg QD as tolerated.
干预措施: tadalafil (Drug)
结局指标
主要结局
Change in Right Ventricular Ejection Fraction
时间窗: Basline and 24 weeks
Effect of dual-upfront therapies versus mono-therapy on percent change of right ventricular function assesed by cardiac MRI (cMRI) at 24 weeks compared with the baseline.
次要结局
- Change in NYHA/WHO Class(Baseline and 48 week)
- B-type Natriuretic Peptide (BNP)(Baseline and 24 weeks)
- 6 Minute Walk Distance(Baseline and 24 weeks)
- N-terminal Pro B-type Natriuretic Peptide (NT-proBNP)(Baseline and 24 weeks)
研究者
Roham T. Zamanian
Principle Investigator
Stanford University