Pulmonary Arterial Hypertension (PAH)ALEPHNCT06987097
Ambrisentan for Early Low-Risk Pulmonary Arterial Hypertension
A study testing Ambrisentan in people with Pulmonary Arterial Hypertension (PAH), run by Nanjing First Hospital, Nanjing Medical University.
Trial summary
This is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled clinical trial. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension (PAH)
- What is being tested?
- Ambrisentan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 410 participants
- Where
- No sites listed yet
- Study dates
- 15 May 2025to 1 Mar 2029
- Phase
- Interventional
- Are there results?
- Not yet: the study is under way
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Age ≥ 18 years;
- mPAP > 20 mmHg and < 25 mmHg, pulmonary vascular resistance (PVR) > 2 WUs and ≤ 3 WUs, and pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg via right heart catheterization (RHC); RHC measurement will be accepted if it was done within 7 days before enrollment;
- Group I PAH, including idiopathic PAH (IPAH), heritable PAH (HPAH), Drug- and toxin-induced PAH, associated with connective tissue disease (connective tissue disease at good control), associated with portal hypertension, associated with congenital heart disease;
- At low risk based on the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension three-strata risk-assessment model;
- The subject or a legally authorized representative must understand the study requirements, agree to the treatment procedures, and provide written informed consent before any study-specific procedures are performed;
- The subject must demonstrate a willingness and ability to comply with all protocol requirements.
Who cannot join
- Patients currently receiving PAH specific medications, regardless of whether mPAP is between 20-25 mmHg. PAH specific medications include endothelin receptor antagonists (ERAs; e.g., bosentan, ambrisentan, macitentan), phosphodiesterase type 5 inhibitors (PDE5i; e.g., sildenafil, tadalafil, vardenafil), prostacyclin analogs (e.g., iloprost, epoprostenol, treprostinil, beraprost), soluble guanylate cyclase stimulators (e.g., riociguat). Intermittent use of PDE5 inhibitors for the treatment of male erectile dysfunction is permitted;
- Intolerance to ambrisentan or its excipients;
- Pulmonary veno-occlusive disease (PVOD);
- Pulmonary capillary hemangiomatosis (PCH);
- Within 6 months after congenital heart disease surgical repair or percutaneous closure procedure;
- Group II-V PH;
Show all 14Show fewer
- Clinically significant anemia, defined as hemoglobin concentration below 75% of the lower limit of normal;
- Renal insufficiency, defined as estimated glomerular filtration rate (eGFR) < 30 mL/min/1.73 m² within 3 months prior to enrollment;
- Elevated Alanine Aminotransferase （ALT） and/or Aspartate Aminotransferase （AST） exceeding 3 times the upper limit of normal (ULN);
- Systolic blood pressure < 85 mmHg;
- Uncontrolled hypertension, defined as blood pressure > 160/90 mmHg at rest and/or > 220/120 mmHg under stress conditions;
- Participation in any clinical drug trial within 4 weeks prior to screening and/or planned participation in another clinical drug trial during this study;
- Expected life expectancy of less than 1 year;
- Pregnant or breastfeeding women.
Trial locations and contacts
No sites are listed yet. Contact the study team or a site near you to ask about taking part.
About this study
Official title: Ambrisentan for the Treatment of Early-Stage Low-Risk Pulmonary Arterial Hypertension: A Multicenter, Randomized, Double-Blind, Placebo-Controlled ALEPH Trial
This is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled clinical trial.
Read the detailed description
Early-stage low-risk PAH is defined as mean pulmonary arterial pressure (mPAP) between 20 and 25 mmHg at rest, measured by right heart catheterization, and classified as low-risk based on the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Patients will be randomized at a 1:1 ratio to either the treatment group (Ambrisentan group) or the control group (Placebo group). Treatment group: Ambrisentan, with an initial dose of 5 mg/day (one tablet per day).Control group: Placebo, which will be provided in the same appearance and taste as Ambrisentan, one tablet per day.
After two weeks of initial treatment, the study drugs' dose will be increased to two tablets per day (10 mg/day). If the patient cannot tolerate the increased dose (e.g., experiencing headache, dizziness, palpitations, hypotension, or other drug-related symptoms or signs), the dose will be reduced to 5 mg/day. If the study drug has reached the maximum allowable dose (two tablets/day) and the patient shows signs of worsening PAH or right heart failure, the clinician may decide to add diuretics (with the type and dosage left at the referring physician's discretion). The number and percentage of patients requiring diuretic combination therapy in both groups will be recorded. Other baseline treatment medications will remain unchanged through follow-up duration.
The study drugs will be administered continuously for 12 months, then unblinding will be performed. Thereafter, patients who have reached the primary endpoint must undertake Ambrisentan. For patients who have not reached the primary endpoint, the subsequent medications treatment will be left at the PAH specialist's discretion. Follow-up will be undertaken at the following timing: Month 1, Month 6, and Month 12, with additional follow-up extending up to 3 years. All clinical drugs involved in this study have completed registration for market approval in China and are currently in clinical use.
- Conditions
- Pulmonary Arterial Hypertension (PAH)
- Being tested
- Ambrisentan, Placebo
- Medical subject headings
- Pulmonary Arterial Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AmbrisentanDrug
After two weeks of initial treatment, the study drugs' dose will be increased to two tablets per day (10 mg/day). If the patient cannot tolerate the increased dose (e.g., experiencing headache, dizziness, palpitations, hypotension, or other drug-related symptoms or signs), the dose will be reduced to 5 mg/day. If the study drug has reached the maximum allowable dose (two tablets/day) and the patient shows signs of worsening PAH or right heart failure, the clinician may decide to add diuretics (with the type and dosage left at the referring physician's discretion). The number and percentage of patients requiring diuretic combination therapy in both groups will be recorded. Other baseline treatment medications will remain unchanged through follow-up duration.
PlaceboDrug
Placebo tablet (one to two tablets corresponding to one to two verum tablets). Administration: Placebo will be administrated orally with or without food intake in the morning.
| Study group | Role | What they receive |
|---|---|---|
| Ambrisentan | Experimental | Monotherapy using ambrisentan will start at a dose of 5 mg (once daily) and will be up-titrated to 10mg (once daily) after 2 weeks apart if patients are tolerable. Receives: Drug: Ambrisentan |
| Placebo Placebo tablet | Placebo comparator | Placebo tablet (one to two tablets corresponding to one to two verum tablets). Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
The primary efficacy endpoint is the composite of pulmonary hypertension progression at 12 months
defined as meeting any of the following criteria within 12 months:
- mPAP ≥ 25 mmHg OR PVR > 3 WUs as measured by RHC OR
- worsening of risk stratification compared to baseline, defining as at least one class progression based on the simplified four-tier model of the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension
Measured: baseline,12 months
Secondary outcomes (22)
systolic PAP (sPAP) by Hemodynamic measurements
Measured: baseline,12 months
mPAP by Hemodynamic measurements
Measured: baseline,12 months
cardiac output (CO) by Hemodynamic measurements
Measured: baseline,12 months
cardiac index (CI) by Hemodynamic measurements
Measured: baseline,12 months
PVR by Hemodynamic measurements
Measured: baseline,12 months
PVRi by Hemodynamic measurements
Measured: baseline,12 months
PAWP by Hemodynamic measurements
Measured: baseline,12 months
right atrial pressure by Hemodynamic measurements
Measured: baseline,12 months
pulmonary arterial compliance by Hemodynamic measurements
Measured: baseline,12 months
diameter of chambers by Echocardiographic measurements
Measured: baseline,12 months
ejection fraction by Echocardiographic measurements
Measured: baseline,12 months
right ventricular (RV) fraction of area change (FAC) by Echocardiographic measurements
Measured: baseline,12 months
TAPSE by Echocardiographic measurements
Measured: baseline,12 months
pulmonary artery accelation time (PAAT) by Echocardiographic measurements
Measured: baseline,12 months
regurgitation of tricuspid or pulmonary valve by Echocardiographic measurements
Measured: baseline,12 months
sPAP by Echocardiographic measurements
Measured: baseline,12 months
RAP by Echocardiographic measurements
Measured: baseline,12 months
WHO functional class through follow - up
Measured: baseline,12 months
Borg index through follow - up
Measured: baseline,12 months
N-terminal-pro BNP
Measured: baseline,12 months
6-minute walk distance (6MWD)
Measured: baseline,12 months
Time to the first occurrence of the following events, analyzed using log-rank and LWYY model
- All-cause mortality
- Hospitalization due to PAH worsening
- Clinical deterioration of PAH, defined as the need for diuretics or digoxin (oral or intravenous), or the need of combination therapy with PAH specific medications
- 6MWD decreases by 10% or 30m
Measured: baseline,12 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted23 May 2025
- Study start15 May 2025 (estimated)
- Primary completion28 Feb 2028 (estimated)
- Study completion1 Mar 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Pulmonary Arterial Hypertension (PAH)Studies of the same condition, open and under way.
- More trials run by Nanjing First Hospital, Nanjing Medical UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 410 participants (estimated)
Sponsor and investigators
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Hang Zhang, Nanjing First Hospital, Nanjing Medical University
- Investigators
- Shao-Liang Chen MD, PhD, Study chair, Nanjing First Hospital, Nanjing Medical University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06987097
- Sponsor's protocol ID
- KY20250327-11
- Acronym
- ALEPH
- Status last verified
- May 2025
- First submitted
- 24 Apr 2025
- Last updated
- 23 May 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Kan JY, Zhang XJ, Yu WD, Yang ZW, Fan FL, Ding GW, Luo J, Li W, Xie DJ, Liu XF, Zhang H, Chen SL. Ambrisentan for Early-Stage Low-Risk Pulmonary Arterial Hypertension: Design of the Randomized, Double-Blind, Placebo-Controlled ALEPH Trial. JACC Asia. 2026 May;6(5):724-732. doi: 10.1016/j.jacasi.2025.12.014. Epub 2026 Feb 7.
PubMed 41653169
Study at a glance
From the registry record, last updated by the sponsor on 23 May 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Ambrisentan for the Treatment of Early-Stage Low-Risk Pulmonary Arterial Hypertension: A Multicenter, Randomized, Double-Blind, Placebo-Controlled ALEPH Trial
- ClinicalTrials.gov ID
- NCT06987097
- Acronym / sponsor ID
- ALEPH / KY20250327-11
- Conditions
- Pulmonary Arterial Hypertension (PAH)
- Study type
- Interventional
- Recruitment status
- Not yet recruiting
- Enrolment
- 410 participants (estimated)
- Lead sponsor
- Nanjing First Hospital, Nanjing Medical UniversityUniversity, hospital or other
- Study start
- 15 May 2025 (estimated)
- Primary completion
- 28 Feb 2028 (estimated)
- Study completion
- 1 Mar 2029 (estimated)
- First posted
- 23 May 2025 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is an investigator-initiated, multicenter, randomized, double-blind, placebo-controlled clinical trial.
Detailed description
Early-stage low-risk PAH is defined as mean pulmonary arterial pressure (mPAP) between 20 and 25 mmHg at rest, measured by right heart catheterization, and classified as low-risk based on the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension. Patients will be randomized at a 1:1 ratio to either the treatment group (Ambrisentan group) or the control group (Placebo group). Treatment group: Ambrisentan, with an initial dose of 5 mg/day (one tablet per day).Control group: Placebo, which will be provided in the same appearance and taste as Ambrisentan, one tablet per day.
After two weeks of initial treatment, the study drugs' dose will be increased to two tablets per day (10 mg/day). If the patient cannot tolerate the increased dose (e.g., experiencing headache, dizziness, palpitations, hypotension, or other drug-related symptoms or signs), the dose will be reduced to 5 mg/day. If the study drug has reached the maximum allowable dose (two tablets/day) and the patient shows signs of worsening PAH or right heart failure, the clinician may decide to add diuretics (with the type and dosage left at the referring physician's discretion). The number and percentage of patients requiring diuretic combination therapy in both groups will be recorded. Other baseline treatment medications will remain unchanged through follow-up duration.
The study drugs will be administered continuously for 12 months, then unblinding will be performed. Thereafter, patients who have reached the primary endpoint must undertake Ambrisentan. For patients who have not reached the primary endpoint, the subsequent medications treatment will be left at the PAH specialist's discretion. Follow-up will be undertaken at the following timing: Month 1, Month 6, and Month 12, with additional follow-up extending up to 3 years. All clinical drugs involved in this study have completed registration for market approval in China and are currently in clinical use.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Ambrisentan | Experimental | Drug: AmbrisentanMonotherapy using ambrisentan will start at a dose of 5 mg (once daily) and will be up-titrated to 10mg (once daily) after 2 weeks apart if patients are tolerable. |
| Placebo Placebo tablet | Placebo comparator | Drug: PlaceboPlacebo tablet (one to two tablets corresponding to one to two verum tablets). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Age ≥ 18 years;
- mPAP > 20 mmHg and < 25 mmHg, pulmonary vascular resistance (PVR) > 2 WUs and ≤ 3 WUs, and pulmonary arterial wedge pressure (PAWP) ≤ 15 mmHg via right heart catheterization (RHC); RHC measurement will be accepted if it was done within 7 days before enrollment;
- Group I PAH, including idiopathic PAH (IPAH), heritable PAH (HPAH), Drug- and toxin-induced PAH, associated with connective tissue disease (connective tissue disease at good control), associated with portal hypertension, associated with congenital heart disease;
- At low risk based on the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension three-strata risk-assessment model;
- The subject or a legally authorized representative must understand the study requirements, agree to the treatment procedures, and provide written informed consent before any study-specific procedures are performed;
Key exclusion criteria (14 listed)
- Patients currently receiving PAH specific medications, regardless of whether mPAP is between 20-25 mmHg. PAH specific medications include endothelin receptor antagonists (ERAs; e.g., bosentan, ambrisentan, macitentan), phosphodiesterase type 5 inhibitors (PDE5i; e.g., sildenafil, tadalafil, vardenafil), prostacyclin analogs (e.g., iloprost, epoprostenol, treprostinil, beraprost), soluble guanylate cyclase stimulators (e.g., riociguat). Intermittent use of PDE5 inhibitors for the treatment of male erectile dysfunction is permitted;
- Intolerance to ambrisentan or its excipients;
- Pulmonary veno-occlusive disease (PVOD);
- Pulmonary capillary hemangiomatosis (PCH);
- Within 6 months after congenital heart disease surgical repair or percutaneous closure procedure;
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| AmbrisentanAfter two weeks of initial treatment, the study drugs' dose will be increased to two tablets per day (10 mg/day). If the patient cannot tolerate the increased dose (e.g., experiencing headache, dizziness, palpitations, hypotension, or other drug-related symptoms or signs), the dose will be reduced to 5 mg/day. If the study drug has reached the maximum allowable dose (two tablets/day) and the patient shows signs of worsening PAH or right heart failure, the clinician may decide to add diuretics (with the type and dosage left at the referring physician's discretion). The number and percentage of patients requiring diuretic combination therapy in both groups will be recorded. Other baseline treatment medications will remain unchanged through follow-up duration. | Drug | Ambrisentan |
| PlaceboPlacebo tablet (one to two tablets corresponding to one to two verum tablets). Administration: Placebo will be administrated orally with or without food intake in the morning. | Drug | Placebo Placebo tablet |
Primary outcome
The primary efficacy endpoint is the composite of pulmonary hypertension progression at 12 months
Time frame: baseline,12 months
defined as meeting any of the following criteria within 12 months: 1. mPAP ≥ 25 mmHg OR PVR > 3 WUs as measured by RHC OR 2. worsening of risk stratification compared to baseline, defining as at least one class progression based on the simplified four-tier model of the 2022 ESC/ERS Guidelines for the diagnosis and treatment of pulmonary hypertension
22 secondary outcomes
systolic PAP (sPAP) by Hemodynamic measurements
Time frame: baseline,12 months
mPAP by Hemodynamic measurements
Time frame: baseline,12 months
cardiac output (CO) by Hemodynamic measurements
Time frame: baseline,12 months
cardiac index (CI) by Hemodynamic measurements
Time frame: baseline,12 months
PVR by Hemodynamic measurements
Time frame: baseline,12 months
PVRi by Hemodynamic measurements
Time frame: baseline,12 months
PAWP by Hemodynamic measurements
Time frame: baseline,12 months
right atrial pressure by Hemodynamic measurements
Time frame: baseline,12 months
pulmonary arterial compliance by Hemodynamic measurements
Time frame: baseline,12 months
diameter of chambers by Echocardiographic measurements
Time frame: baseline,12 months
ejection fraction by Echocardiographic measurements
Time frame: baseline,12 months
right ventricular (RV) fraction of area change (FAC) by Echocardiographic measurements
Time frame: baseline,12 months
TAPSE by Echocardiographic measurements
Time frame: baseline,12 months
pulmonary artery accelation time (PAAT) by Echocardiographic measurements
Time frame: baseline,12 months
regurgitation of tricuspid or pulmonary valve by Echocardiographic measurements
Time frame: baseline,12 months
sPAP by Echocardiographic measurements
Time frame: baseline,12 months
RAP by Echocardiographic measurements
Time frame: baseline,12 months
WHO functional class through follow - up
Time frame: baseline,12 months
Borg index through follow - up
Time frame: baseline,12 months
N-terminal-pro BNP
Time frame: baseline,12 months
6-minute walk distance (6MWD)
Time frame: baseline,12 months
Time to the first occurrence of the following events, analyzed using log-rank and LWYY model
Time frame: baseline,12 months
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 23 May 2025.
- Derived from this study: PubMed 41653169Kan JY, Zhang XJ, Yu WD, Yang ZW, Fan FL, Ding GW, Luo J, Li W, Xie DJ, Liu XF, Zhang H, Chen SL. Ambrisentan for Early-Stage Low-Risk Pulmonary Arterial Hypertension: Design of the Randomized, Double-Blind, Placebo-Controlled ALEPH Trial. JACC Asia. 2026 May;6(5):724-732. doi: 10.1016/j.jacasi.2025.12.014. Epub 2026 Feb 7.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part.
Shao-Liang Chen MD, PhD study chair
Nanjing First Hospital, Nanjing Medical University
Questions about this trial
What is this clinical trial studying?
A study testing Ambrisentan in people with Pulmonary Arterial Hypertension (PAH), run by Nanjing First Hospital, Nanjing Medical University.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 6 inclusion and 14 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: opening soon, as of the sponsor's last update on 23 May 2025. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Han Zhang MD, PhD (+86-25-52271330, dxh_nari@sina.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
The primary efficacy endpoint is the composite of pulmonary hypertension progression at 12 months (time frame: baseline,12 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06987097, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 23 May 2025.