NCT00303459已完成4 期
Effects of Combination of Bosentan and Sildenafil Versus Sildenafil Monotherapy on Morbidity and Mortality in Symptomatic Patients With Pulmonary Arterial Hypertension - A Multicenter, Double-blind, Randomized, Placebo-controlled, Parallel Group, Prospective, Event Driven Phase IV Study
Actelion0 个研究点目标入组 334 人开始时间: 2006年5月最近更新:
适应症
干预措施
相关药物
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 发起方
- 入组人数
- 334
- 主要终点
- Time to First Confirmed Morbidity/Mortality Event up to the End of Study
研究概览
简要总结
COMPASS-2 is a Phase 4, prospective, randomized, double-blind, placebo-controlled, event-driven study evaluating the effect of bosentan on the time to first confirmed morbidity/mortality event in patients with symptomatic PAH already receiving sildenafil therapy. Patients must have been receiving doses of sildenafil equal to or greater than 20 mg t.i.d. for at least 12 weeks prior to being randomized.
The study continued until the predefined target number of morbidity/mortality events was reached.
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
- 12 Years 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent prior to initiation of any study-mandated procedure
- •Males or females >=12 years of age (except for countries where this age limit is contrary to specific regulatory requirements).
- •Women of childbearing potential must have a negative pretreatment pregnancy test and must use a reliable method of contraception during study treatment and for at least 3 months after study treatment termination.
- •·Reliable methods of contraception are:
- •O Barrier type devices (e.g., female condom, diaphragm, contraceptive sponge) only in combination with a spermicide.
- •O Intrauterine devices. O Oral, transdermal, injectable or implantable contraceptives only in combination with a barrier method.
- •Hormone-based contraceptives alone, regardless of the route of administration, are not considered as reliable methods of contraception.
- •Abstention, rhythm method, and contraception by the partner alone are not acceptable methods of contraception.
- •Women not of childbearing potential are defined as postmenopausal (i.e., amenorrhea for at least 1 year), or documented surgically or naturally sterile.
- •Patients with symptomatic PAH
- •Patients with the following types of PAH belonging to WHO Group I:
- •Idiopathic (IPAH)
- •Familial (FPAH)
- •Associated with (APAH):
- •i. Collagen vascular disease with normal left ventricular function (ejection fraction (EF) > 50%) ii. Congenital systemic-to-pulmonary shunts at least 2 years post surgical repair iii. Drugs and toxins
- •PAH diagnosed by right heart catheter showing:
- •Mean pulmonary arterial pressure (mPAP) >= 25 mm Hg AND
- •Pulmonary capillary wedge pressure (PCWP) =< 15 mm Hg or left ventricular end diastolic pressure (LVEDP) =< 15 mmHg If both PCWP and LVEDP are available then the LVEDP value is retained for inclusion.
- •Treatment with a stable dose of sildenafil equal to or greater than 20 mg t.i.d. for at least 12 weeks prior to randomization (no sildenafil dosage adjustment should occur in this period) 7)150 m =< 6-minute walk test (6MWT) =< 480 m, documented by 2 tests with second 6MWT within 15% of first 6MWT distance or a third test required
- •Exclusion Criteria :
- •PAH belonging to WHO group II-V
- •PAH associated with portal hypertension and HIV infection
- •PAH associated with thyroid disorders, glycogen storage disease, Gaucher disease, hereditary hemorrhagic telangiectasia, hemoglobinopathies, myeloproliferative disorders and splenectomy
- •PAH associated with significant venous or capillary involvement (PCWP > 15 mmHg): pulmonary veno-occlusive disease and pulmonary capillary hemangiomatosis
- •Persistent pulmonary hypertension of the newborn
- •Significant valvular disease with valvular lesions to be excluded by echocardiogram within 2 years prior to randomization (i.e. patients with tricuspid or pulmonary insufficiency secondary to PAH can be included)
- •Restrictive lung disease: total lung capacity (TLC) < 60% of normal predicted value (see Appendix 3)
- •Obstructive lung disease: forced expiratory volume/forced vital capacity (FEV1/FVC) < 0.5
- •Moderate to severe hepatic impairment, i.e., Child-Pugh Class B or C
- •Known HIV infection
- •Acute or chronic impairment (other than dyspnea), limiting the ability to comply with study requirements or that may interfere with the safety or the evaluation of the study, such as chronic infection, chronic renal failure etc.
- •Psychotic, addictive or other disorder limiting the ability to provide informed consent or to comply with study requirements
- •Pregnancy or breast-feeding
- •Condition that prevents compliance with the protocol or adherence to therapy
- •Systolic blood pressure < 85 mmHg
- •Body weight < 40 kg
- •Hemoglobin <75% of the lower limit of the normal range
- •Aspartate aminotransferase (AST) and/or alanine aminotransferase (ALT) > 1.5 times the upper limit of normal ranges
- •Known hypersensitivity or history of drug-related adverse events with bosentan (e.g. increase in liver function test results), or any of the excipients of its formulation
- •Receipt of an investigational product other than sildenafil within 3 months before start of study treatment
- •Treatment with endothelin receptor antagonists (ERAs), prostanoids or phosphodiesterase (PDE) 5 inhibitors other than sildenafil within 3 months prior to randomization
- •Concomitant systemic treatment within 1 week prior to randomization with
- •calcineurin inhibitors (e.g., cyclosporine A and tacrolimus), sirolimus and everolimus
- •glibenclamide (glyburide)
- •both cytochrome P2C9 (CYP2C9) and cytochrome P3A4 (CYP3A4) (e.g., fluconazole, amiodarone, voriconazole)
- •combination of drugs that inhibit CYP2C9 and CYP3A4
- •Treatment with nitrates and alpha-blockers at time of randomization
- •In the opinion of the investigator - patients in need for treatment with any prostanoid up to Visit 4
- •Significant left ventricular dysfunction
排除标准
- 未提供
研究组 & 干预措施
A
Experimental
Bosentan
干预措施: bosentan (Drug)
B
Placebo Comparator
Placebo
干预措施: placebo (Drug)
结局指标
主要结局
Time to First Confirmed Morbidity/Mortality Event up to the End of Study
时间窗: From baseline to end of study, approximately 86 months
Kaplan-Meier estimate of percentage of participants without a morbidity/mortality event. A morbidity/mortality event is defined as the occurrence of a) death, b) hospitalization for worsening or complication of PAH or intravenous prostanoid initiation, c) atrial septostomy, d) lung transplantation, or e) worsening PAH, defined as "moderately" or "markedly" worsened PAH symptoms using a patient global self-assessment (PGSA) scale AND initiation of inhaled or subcutaneous prostanoids or the disease progression package (open-label bosentan). If a patient replied "no change" or "mildly worse" on the PGSA, a decrease in 6MWT of 20% versus last visit or 30% versus baseline is also required to confirm the event.
次要结局
- Time to First Confirmed Death, Hospitalization for Worsening or Complication of PAH or Initiation of Intravenous Prostanoids, Atrial Septostomy, or Lung Transplantation(Baseline to end of study, approximately 86 months)
- Change From Baseline to Week 16 in 6 Minute Walk Test (6MWT)(From baseline to week 16)
- Time to Death of All Causes From Baseline to End of Study(Baseline to End of Study, approximately 86 months)
- Number of Participants With Improved, No Change, or Worsened World Health Organisation Functional Class From Baseline to Week 16(From baseline to Week 16)
- Adjusted Percentage Ratio From Baseline in N-terminal Pro-B-type Natriuretic Peptide (NT-pro-BNP)(Baseline to Month 20)
- Change From Baseline to Week 16 in Borg Dyspnea Index(Baseline to Week 16)
- Change From Baseline to Week 16 in the EuroQol 5 Dimensions (EQ-5D) Visual Analogue Scale Score(Baseline to Week 16)
- Patient Global Self Assessment (PGSA) Status at Week 16(Week 16)
- Change From Baseline to Week 16 in the EuroQol 5 Dimensions (EQ-5D) Questionnaire Calculated Score(From baseline to Week 16)
研究者
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进行中（未招募）
不适用
Effects of combination of bosentan and sildenafil versus sildenafil monotherapy on morbidity and mortality in symptomatic patients with pulmonary arterial hypertension – A multicenter, double - blind, randomized, placebo - controlled, parallel group, prospective, event driven Phase IV study - COMPASS 2Patients to be included must have PAH belonging to WHO Group I, in agreement with the approved indications for sildenafil in PAH by the US FDA:a.Idiopathic (IPAH)b.Familial (FPAH)c.Associated with (APAH):i.Collagen vascular disease with normal left ventricular function (ejection fraction (EF) > 50%) ii.Congenital systemic-to-pulmonary shunts at least 2 years post surgical repairiii.Drugs and toxinsMedDRA version: 9.1Level: LLTClassification code 10064908Term: Associated with (APAH)MedDRA version: 9.1Level: LLTClassification code 10064909Term: Idiopathic (IPAH)MedDRA version: 9.1Level: LLTClassification code 10064910Term: Familial (FPAH)EUCTR2005-005068-97-SEActelion Pharmaceuticals Ltd.350
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