2026-525351-81-00招募中2 期
DIRECTION- Discontinuation versus continuation of riociguat monotherapy in chronic thromboembolic pulmonary hypertension successfully treated with balloon pulmonary angioplasty
适应症
相关药物
试验速览
- 阶段
- 2 期
- 状态
- 招募中
- 入组人数
- 150
- 试验地点
- 23
- 主要终点
- clinical worsening at the longest follow-up: a.death due to any cause, b.hospitalization due to worsening of PH, including: i.Documented right heart failure, OR ii.Need for lung transplantation, OR iii.Need for intravenous diuretics and/or inotropic support, OR iv. Need for parental prostanoids c. decline in 6MWD by ≥15% from baseline, combined with WHO functional class III or IV IV(confirmed on a second test within 7 days and both conditions met)
研究概览
简要总结
To estimate, using a Bayesian analysis, the risk of clinical worsening associated with discontinuation of riociguat monotherapy after successful BPA in CTEPH patients over a follow-up period of at least 12 months, compared with continuation, as assessed by the primary endpoint.
入排标准
- 年龄范围
- 18 years 至 65+ years（18-64 Years, 65+ Years）
- 接受健康志愿者
- 否
入选标准
- •Signed informed consent and willingness to accept either riociguat monotherapy discontinuation or continuation
- •Adults ≥18 years
- •Patients diagnosed with inoperable CTEPH or persistent PH after PEA who have achieved therapeutic goals following BPA: a. WHO FC I or II b. PVR < 3 Wood units c. Mean pulmonary artery pressure (mPAP) < 30 mmHg
- •Riociguat monotherapy for ≥6 months with stable doses for ≥3 months prior to enrollment
- •Last BPA session performed ≥6 months prior to enrollment
- •TM6 ≥ 150 m
- •For women of childbearing potential : highly effective contraception
排除标准
- •Background treatment with any PH therapy, except for riociguat, (e.g., any endothelin receptor antagonist (ERA), phosphodiesterase-5 inhibitor (PDE-5i), parenteral prostanoids, prostacyclin receptor agonist)
- •Significant obstructive or restrictive lung disease, defined as: FEV₁ < 60% of predicted, with FEV₁/FVC < 65% and/or total lung capacity (TLC) < 60% of predicted, or known significant chronic lung disease diagnosed via imaging (e.g., interstitial lung disease, emphysema)
- •Severe hepatic impairment, defined as: Child-Pugh class B or C and/or liver aminotransferase levels > 3× upper limit of normal (ULN)
- •Severe renal impairment (estimated creatinine clearance ≤ 30 mL/min/1.73 m²)
- •Left heart failure with left ventricular ejection fraction (LVEF) < 40%
- •Ongoing or planned treatment with organic nitrates.
- •Treatment with strong cytochrome P450 3A4 (CYP3A4) inducers (e.g., rifabutin, rifampicin, carbamazepine, phenobarbital, phenytoin, St. John’s wort)
- •Treatment with strong multi pathway P-glycoprotein (P-gp)/ breast cancer resistance protein (BCRP) inhibitors (e.g., lopinavir/ritonavir).
- •Persons deprived of their liberty by judicial or administrative decision
- •Persons under psychiatric care without their consent, refer to articles L.3212-1, L.3213-1 and L.1121-8 persons admitted to a health or social institution for purposes other than research
- •Adults subject to a legal protection measure (guardianship, curatorship, etc.),
- •Treatment with a strong CYP3A4 inhibitor (e.g., ketoconazole, itraconazole, voriconazole, clarithromycin, telithromycin, nefazodone, ritonavir, and saquinavir) or a moderate dual CYP3A4/CYP2C9 inhibitor (e.g., fluconazole, amiodarone) or co-administration of a combination of moderate CYP3A4 and moderate CYP2C9 inhibitors.
- •Persons unable to give their consent
- •Persons who are not affiliated to a social security scheme or who are beneficiaries of such a scheme
- •History of life-threatening hemoptysis (>100 mL within 24 hours) or prior bronchial artery embolization for hemoptysis
- •Pregnancy, breastfeeding, or intention to become pregnant during the study period
- •Severe comorbidities or underlying conditions with an anticipated life expectancy < 12 months, including active malignancy with localized or metastatic disease
- •Alcohol abuse, as determined by the investigator
- •Any condition or factor likely to interfere with protocol compliance, in the opinion of the investigator
- •Participation in another interventional trial or being in the exclusion period following a previous research involving the human person
- •Post-capillary pulmonary hypertension, defined as pulmonary artery wedge pressure (PAWP) > 15 mmHg
结局指标
主要结局
clinical worsening at the longest follow-up: a.death due to any cause, b.hospitalization due to worsening of PH, including: i.Documented right heart failure, OR ii.Need for lung transplantation, OR iii.Need for intravenous diuretics and/or inotropic support, OR iv. Need for parental prostanoids c. decline in 6MWD by ≥15% from baseline, combined with WHO functional class III or IV IV(confirmed on a second test within 7 days and both conditions met)
clinical worsening at the longest follow-up: a.death due to any cause, b.hospitalization due to worsening of PH, including: i.Documented right heart failure, OR ii.Need for lung transplantation, OR iii.Need for intravenous diuretics and/or inotropic support, OR iv. Need for parental prostanoids c. decline in 6MWD by ≥15% from baseline, combined with WHO functional class III or IV IV(confirmed on a second test within 7 days and both conditions met)
次要结局
- Change from baseline to Months 3, 6,12 and every 6 months until the last enrolled patient has completed the minimum 12-month follow-up in 6MWD, WHO FC, NT-proBNP levels, and quality of life measured by the generic EQ-5D-5L and the disease-specific EmPHasis-10.
- Change from baseline to Month 12 in right atrial pressure, mPAP, cardiac output and PVR.
- Health economic outcomes: incremental cost effectiveness ratio (difference in costs/difference in QALYS) of riociguat monotherapy withdrawal for the French public health system.
- Treatment burden assessed at baseline and Month 12
- Occurrence at the longest follow-up (minimum 12 months) of individual components of the primary endpoint
研究者
Mitja Jevnikar
Scientific
Assistance Publique Hopitaux De Paris
研究点 (23)
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