Phase 3, Multicenter, Randomized, Double-blind, Placebo Controlled Withdrawal Study of Pulmonary Arterial Hypertension(PAH) Subjects With LTOT Use That Have Demonstrated Improved Exercise Tolerance With the Use of Inhaled Nitric Oxide (INO)
试验速览
- 阶段
- 3 期
- 状态
- 撤回
- 发起方
- 试验地点
- 4
- 主要终点
- Time to clinical worsening during iNO withdrawal for up to 8 weeks
研究概览
简要总结
Study of PAH Subjects with LTOT Use that have Demonstrated Improved Exercise Tolerance with the use of Inhaled Nitric Oxide
详细描述
Phase 3, Multicenter, Randomized, Double-blind, Placebo Controlled Withdrawal Study of Pulmonary Arterial Hypertension(PAH) Subjects with LTOT Use that have Demonstrated Improved Exercise Tolerance with the use of Inhaled Nitric Oxide (INO)
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)
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
- •Signed Informed Consent Form prior to the initiation of any study mandated procedures or assessments
- •Subjects must be enrolled in the PULSE PAH-004 clinical trial and must have been on LTOT and on open-label treatment with iNO 75 mcg/kg IBW/hr for at least 4 months
- •Subjects must have achieved ≥ 30 meter improvement in 6MWD after 4, 8 or 12 months of open-label treatment with iNO 75 mcg/kg IBW/hr as compared to either their PULSE PAH-004 Week 2 end of Run-in OR End of Study (EOS)in PULSE-PAH-
- •Subjects are willing and considered in the judgement of the Investigator able to use the INOpulse device continuously for up to 24 hours per day
- •Female subjects of childbearing potential must have a negative pregnancy test (serum or urine) at randomization. All female subjects must use an effective method of birth control to avoid pregnancy.
排除标准
- •Subjects with episodes of worsening of PAH in the last 30 days prior to PULSE PAH-007 Baseline/Randomization
- •Subjects that experience Pulmonary Rebound in PULSE-PAH-004
- •Change in dose or types of PAH specific therapies in the last 30 days prior to Baseline/Randomization
- •Subjects who require treatment with riociguat
- •Subjects who early discontinued drug/device usage due to withdrawal of consent or an adverse event requiring termination from treatment in PULSE PAH-004
- •Women who are pregnant
- •The concurrent use of the INOpulse device with a continuous airway pressure (CPAP), Bilevel Positive Airway Pressure (BiPAP, or any other positive pressure device.
研究组 & 干预措施
Cohort 1: Placebo 99.999% Nitrogen
Randomized Withdrawal Treatment Period Week 1-8:
Placebo at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day
Long Term Open Label Extension Period:
iNO at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day
干预措施: Placebo (Drug)
Cohort 1: Placebo 99.999% Nitrogen
Randomized Withdrawal Treatment Period Week 1-8:
Placebo at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day
Long Term Open Label Extension Period:
iNO at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day
干预措施: iNO (Drug)
Cohort 2: iNO 75 mcg/kg IBW/hr
Randomized Withdrawal Treatment Period Week 1-8:
iNO at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day
Long Term Open Label Extension Period:
iNO at a dose setting of 75 mcg/kg IBW/hr for up to 24 hr/day
干预措施: iNO (Drug)
结局指标
主要结局
Time to clinical worsening during iNO withdrawal for up to 8 weeks
时间窗: 8 weeks
A clinical worsening event is defined as: 1. Death (all-cause mortality) 2. Atrial septostomy 3. Hospitalization due to worsening of PAH 4. Need to start additional specific PAH treatment 5. Decrease of \>15% in 6 Minute Walk Distance from randomization into the study 6. Worsening of WHO Functional Class (e.g., from Class II to Class III or IV, OR Class III to Class IV)
次要结局
- Difference in clinical worsening events that occur during iNO withdrawal for up to 8 weeks between those treated with iNO ≥ 10 months prior to the start of withdrawal of iNO vs. those treated < 10 months prior to initiation of withdrawal to iNO.(8 weeks)