이 페이지는 자동 번역되었으며 번역의 정확성을 보장하지 않습니다. 참조하십시오 영문판 원본 텍스트의 경우.

Randomized Study of Triple Therapy vs Sildenafil Dose Optimization in Pulmonary Arterial Hypertension (ASCEND-PAH)

2026년 7월 28일 업데이트: Caio Júlio César dos Santos Fernandes, University of Sao Paulo General Hospital

A Prospective, Randomized, Open-Label Study Comparing Triple Therapy Versus Sildenafil Dose Optimization in Patients With Pulmonary Arterial Hypertension Using COMPERA 2.0 Risk Stratification as the Primary Outcome

Pulmonary arterial hypertension (PAH) is a rare and progressive disease characterized by increased pressure in the pulmonary arteries, leading to right heart failure and premature death. Although combination therapy has improved outcomes, many patients remain at intermediate or high clinical risk despite treatment.

When patients do not reach low-risk status, treatment escalation is recommended. However, different escalation strategies are used in clinical practice, including increasing the dose of existing medications or adding a third drug that targets a different biological pathway. There is limited prospective randomized evidence directly comparing these approaches.

The ASCEND-PAH study is a prospective, randomized, open-label clinical trial designed to compare two therapeutic escalation strategies in adults with PAH who remain at intermediate or high risk despite dual therapy with an endothelin receptor antagonist and sildenafil. Participants will be randomized to either: (1) escalation to triple therapy with the addition of a prostacyclin pathway agent, or (2) optimization of dual therapy by increasing the dose of sildenafil.

The primary objective is to compare the proportion of patients who improve their risk category according to the COMPERA 2.0 four-stratum risk model within 3 to 6 months after randomization. Secondary outcomes include changes in functional status, exercise capacity, biomarkers, clinical worsening, safety, and treatment persistence

연구 개요

상태

모병

정황

개입 / 치료

상세 설명

This is a prospective, randomized, open-label, parallel-group clinical trial designed to evaluate therapeutic escalation strategies in adults with pulmonary arterial hypertension (PAH, Group 1) who remain at intermediate-low, intermediate-high, or high risk according to the COMPERA 2.0 four-stratum model despite stable dual therapy.

Eligible participants must be receiving an endothelin receptor antagonist in combination with sildenafil and have a clinical indication for treatment escalation. After confirmation of eligibility and baseline assessments, participants will be randomized in a 1:1 ratio to one of two strategies:

Escalation to triple therapy through addition of a prostacyclin pathway agent (inhaled iloprost or selexipag), according to clinical judgment and availability.

Optimization of dual therapy by increasing the dose of sildenafil according to clinical practice.

Baseline assessments may include WHO functional class, 6-minute walk distance, and BNP or NT-proBNP levels obtained within 90 days prior to randomization. Follow-up evaluation will occur between 3 and 6 months after randomization, with the primary analysis based on the assessment closest to 6 months within that window.

The primary endpoint is the proportion of patients who achieve improvement in risk stratification, defined as a decrease of at least one risk category according to the COMPERA 2.0 four-stratum model. Secondary endpoints include composite clinical improvement and worsening, change in individual clinical parameters, time to clinical worsening, safety outcomes, need for additional therapeutic escalation, and treatment persistence.

The study is powered to detect a clinically meaningful absolute difference of 20 percentage points in risk improvement between groups, with planned enrollment of approximately 196 participants to account for potential losses to follow-up

연구 유형

중재적

등록 (추정된)

196

단계

  • 4단계

연락처 및 위치

이 섹션에서는 연구를 수행하는 사람들의 연락처 정보와 이 연구가 수행되는 장소에 대한 정보를 제공합니다.

연구 연락처

연구 장소

  • 브라질
    • São Paulo
      • São Paulo, São Paulo, 브라질, 04551-060
        • 모병
        • Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo
        • 연락하다:

참여기준

연구원은 적격성 기준이라는 특정 설명에 맞는 사람을 찾습니다. 이러한 기준의 몇 가지 예는 개인의 일반적인 건강 상태 또는 이전 치료입니다.

자격 기준

공부할 수 있는 나이

  • 성인
  • 고령자

건강한 자원 봉사자를 받아들입니다

아니

설명

Inclusion Criteria:

  • Age ≥18 years
  • Diagnosis of pulmonary arterial hypertension (PAH, Group 1) confirmed according to accepted clinical and hemodynamic criteria
  • Stable treatment with an endothelin receptor antagonist in combination with sildenafil prior to randomization
  • Classified as intermediate-low, intermediate-high, or high risk according to the COMPERA 2.0 four-stratum model
  • Clinical indication for therapeutic escalation
  • Availability for follow-up assessment between 3 and 6 months after randomization
  • Ability to provide written informed consent

Exclusion Criteria:

  • Participation in another interventional clinical trial that mandates treatment modification
  • Known contraindication to prostacyclin pathway agents (including iloprost or selexipag)
  • Known contraindication to sildenafil dose escalation
  • Pregnancy or breastfeeding
  • Women of childbearing potential not using effective contraception
  • Any clinical condition that, in the investigator's judgment, would interfere with study participation or outcome assessment

공부 계획

이 섹션에서는 연구 설계 방법과 연구가 측정하는 내용을 포함하여 연구 계획에 대한 세부 정보를 제공합니다.

연구는 어떻게 설계됩니까?

디자인 세부사항

  • 주 목적: 치료
  • 할당: 무작위
  • 중재 모델: 병렬 할당
  • 마스킹: 없음(오픈 라벨)

무기와 개입

참가자 그룹 / 팔
개입 / 치료
활성 비교기: Sildenafil Dose Optimization
Participants will continue dual therapy with an endothelin receptor antagonist and sildenafil, with optimization of sildenafil dose according to clinical practice. No additional pulmonary arterial hypertension pathway agent will be added at randomization. Treatment adjustments after randomization will be recorded if clinically required.
의약품: Sildenafil Dose Optimization
Optimization of sildenafil dose within approved dosing ranges as part of dual therapy with an endothelin receptor antagonist. Dose adjustments will be performed according to clinical practice to achieve maximal tolerated and guideline-recommended dosing without addition of a new PAH pathway agent at randomization.
다른 이름들:
  • 실데나필
실험적: Triple Therapy Escalation (Inhaled Iloprost or Selexipag)
Participants will receive escalation to triple therapy through addition of a prostacyclin pathway agent (inhaled iloprost or selexipag) to ongoing dual therapy with an endothelin receptor antagonist and sildenafil. The specific prostacyclin pathway agent will be selected according to clinical judgment and availability. Participants will remain on triple therapy during follow-up unless modification is clinically indicated.
의약품: Prostacyclin Pathway Agent
Addition of a prostacyclin pathway agent (inhaled iloprost or oral selexipag) to ongoing dual therapy with an endothelin receptor antagonist and sildenafil as part of therapeutic escalation to triple therapy. The specific agent will be selected according to clinical judgment and availability. Dosing will follow approved labeling and routine clinical practice.
다른 이름들:
  • 셀렉시팍
  • 일로프로스트

연구는 무엇을 측정합니까?

주요 결과 측정

결과 측정
측정값 설명
기간
Improvement in Risk Stratification According to the COMPERA 2.0 Four-Stratum Model
기간: Between 3 and 6 months after randomization (assessment closest to 6 months within the predefined window)
Proportion of participants who achieve improvement in clinical risk category between baseline and follow-up, defined as a decrease of at least one risk category according to the COMPERA 2.0 four-stratum model (low, intermediate-low, intermediate-high, high risk). Risk status is determined using World Health Organization functional class, 6-minute walk distance, and BNP or NT-proBNP levels, when available.
Between 3 and 6 months after randomization (assessment closest to 6 months within the predefined window)

2차 결과 측정

결과 측정
측정값 설명
기간
Composite Clinical Improvement at 3-6 Months
기간: Between 3 and 6 months after randomization
Proportion of participants who achieve composite clinical improvement between baseline and follow-up (3-6 months), defined as improvement in at least two of the following without worsening in any: (1) improvement of ≥1 WHO functional class; (2) increase of ≥30 meters in 6-minute walk distance; (3) reduction of ≥30% in BNP or NT-proBNP levels.
Between 3 and 6 months after randomization
Composite Clinical Worsening
기간: From randomization through 6 months of follow-up
Occurrence of clinical worsening defined as any of the following during follow-up: worsening of ≥1 WHO functional class; decrease of ≥30 meters in 6-minute walk distance; increase of ≥30% in BNP or NT-proBNP; need for additional therapeutic escalation; hospitalization related to pulmonary arterial hypertension; or death from any cause.
From randomization through 6 months of follow-up
Change in WHO Functional Class
기간: Between 3 and 6 months after randomization
Change in World Health Organization (WHO) functional class between baseline and follow-up. WHO functional class ranges from I (least severe) to IV (most severe), with higher classes indicating worse functional limitation.
Between 3 and 6 months after randomization
Change in 6-Minute Walk Distance (6MWD)
기간: Between 3 and 6 months after randomization
Absolute change in 6-minute walk distance (meters) between baseline and follow-up assessment.
Between 3 and 6 months after randomization
Change in BNP or NT-proBNP Levels
기간: Between 3 and 6 months after randomization
Percent change in BNP or NT-proBNP levels between baseline and follow-up. Higher values indicate greater cardiac strain and worse prognosis.
Between 3 and 6 months after randomization
Time to Clinical Worsening
기간: From randomization through 6 months of follow-up
Time from randomization to first occurrence of clinical worsening event as defined in the composite clinical worsening outcome.
From randomization through 6 months of follow-up
Treatment Persistence
기간: From randomization through 6 months of follow-up
Proportion of participants who remain on their initially assigned therapeutic strategy without permanent discontinuation by the follow-up visit.
From randomization through 6 months of follow-up
Safety and Adverse Events
기간: From randomization through 6 months
Incidence, type, and severity of adverse events and serious adverse events occurring during the study period.
From randomization through 6 months

공동 작업자 및 조사자

여기에서 이 연구와 관련된 사람과 조직을 찾을 수 있습니다.

스폰서

University of Sao Paulo General Hospital

수사관

  • 수석 연구원: Caio Fernandes, Instituto do Coração (InCor), Hospital das Clínicas HCFMUSP, Faculdade de Medicina, Universidade de São Paulo

연구 기록 날짜

이 날짜는 ClinicalTrials.gov에 대한 연구 기록 및 요약 결과 제출의 진행 상황을 추적합니다. 연구 기록 및 보고된 결과는 공개 웹사이트에 게시되기 전에 특정 품질 관리 기준을 충족하는지 확인하기 위해 국립 의학 도서관(NLM)에서 검토합니다.

연구 주요 날짜

연구 시작 (추정된)

2026년 7월 22일

기본 완료 (추정된)

2028년 7월 1일

연구 완료 (추정된)

2028년 12월 31일

연구 등록 날짜

최초 제출

2026년 7월 14일

QC 기준을 충족하는 최초 제출

2026년 7월 14일

처음 게시됨 (실제)

2026년 7월 20일

연구 기록 업데이트

마지막 업데이트 게시됨 (실제)

2026년 7월 30일

QC 기준을 충족하는 마지막 업데이트 제출

2026년 7월 28일

마지막으로 확인됨

2026년 7월 1일

추가 정보

이 연구와 관련된 용어

키워드

추가 관련 MeSH 약관

기타 연구 ID 번호

  • CAAE: 97708926.6.0000.0068

개별 참가자 데이터(IPD) 계획

개별 참가자 데이터(IPD)를 공유할 계획입니까?

미정

약물 및 장치 정보, 연구 문서

미국 FDA 규제 의약품 연구

아니

미국 FDA 규제 기기 제품 연구

아니

이 정보는 변경 없이 clinicaltrials.gov 웹사이트에서 직접 가져온 것입니다. 귀하의 연구 세부 정보를 변경, 제거 또는 업데이트하도록 요청하는 경우 register@clinicaltrials.gov. 문의하십시오. 변경 사항이 clinicaltrials.gov에 구현되는 즉시 저희 웹사이트에도 자동으로 업데이트됩니다. .

구독하다