Pulmonary Arterial Hypertension (PAH)Phase 3COMMODITIESNCT07245680
COMMODITIES Trial: Initial Dual Oral Therapy vs Monotherapy in PAH With Cardiovascular Comorbidities
A Phase 3 study testing Tadalafil and Ambrisentan in people with Pulmonary Arterial Hypertension (PAH) and Comorbidities, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
Trial summary
Pulmonary arterial hypertension (PAH) is a rare, progressive disease associated with poor prognosis, especially in patients with cardiovascular comorbidities. Current guidelines recommend initial combination therapy, but evidence is lacking for patients with significant comorbidities who are often excluded from… Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Pulmonary Arterial Hypertension (PAH), Comorbidities, Cardiovascular Disease (CVD)
- What is being tested?
- Tadalafil and Ambrisentan
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 186 participants
- Where
- 1 siteFrance
- Study dates
- 28 Apr 2026to 14 Feb 2029
- Phase
- Phase 3
- 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
- Initial PAH diagnosis < 6 months preceding randomisation
- Negative vasoreactivity test
- Treatment-naïve PAH (group 1): idiopathic, heritable, associated with drugs and toxin, associated with connective tissue disease, HIV infection or systemic-to-pulmonary congenital shunt corrected for more than one year
- Meet all of the following hemodynamic criteria by means of a RHC prior to screening:
- mPAP≥25 mmHg and
- PAWP<15 mmHg and
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- with PVR≥3 WU
- Presence of at least two of the following criteria, as listed in the European pulmonary hypertension guidelines:
- History of essential hypertension
- Diabetes mellitus (any type)
- Obesity (defined by a BMI ≥30 kg/m2)
- Coronary heart disease (established by any of the following: history of myocardial infarction, history of percutaneous coronary intervention, angiographic evidence of coronary artery disease (>50% stenosis in ≥1 vessel), positive ST, previous coronary artery bypass graft, stable angina)
- Participant able to understand the study procedures
- For women of childbearing potential (WOCBP), effective form of contraception* from screening up to 1 month following discontinuation of the last study treatment
- Affiliation to the french social security regime
- Signed written informed consent
Who cannot join
- Porto-pulmonary hypertension
- Uncorrected systemic-to-pulmonary congenital shunt
- Evidence of thromboembolic disease assessed by ventilation perfusion (V/Q) lung scan or CT pulmonary angiography
- Patients listed for lung or heart-lung transplantation at time of screening
- Patients on any PAH-specific drug therapy at any time preceding randomisation
- Known moderate-to-severe restrictive lung disease (i.e., total lung capacity < 60% of predicted value) or obstructive lung disease (i.e., forced expiratory volume in one second [FEV1] < 60% of predicted, with FEV1 / forced vital capacity < 65%) or known significant chronic lung disease diagnosed by chest imaging (e.g., interstitial lung disease, emphysema).
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- Known or suspected pulmonary veno-occlusive disease (PVOD)
- Severe renal insufficiency (creatinine clearance < 30 mL/min)
- Documented severe hepatic impairment (with or without cirrhosis) according to National Cancer Institute organ dysfunction working group criteria, defined as total bilirubin > 3 x ULN or serum AST and/or ALT > 3xULN (assessed by local laboratory at screening) and/or Child-Pugh Class C.
- Haemoglobin < 10 g/dL
- Patient under guardianship curatorship, deprived of liberty
- Pregnant women, or breast-feeding women
- Treatment with other PDE-5i for erectile dysfunction
- Ongoing or planned treatment with nitrates and/or doxazosin.
- Ongoing or planned treatment with riociguat
- Treatment with strong inducers of CYP3A4 (e.g., carbamazepine, rifampin, rifampicin, rifabutin, rifapentin, phenobarbital, phenytoin, and St. John's wort) ≤28 days preceding randomisation
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
France1 site, 1 recruiting
- Recruiting
Hôpital Bicêtre -Service de pneumologie et soins intensifs respiratoires
Le Kremlin-Bicêtre, 94270
Laurent SAVALE, Md, PhD, +33 (0)1 45 21 79 08, laurent.savale@aphp.fr
About this study
Official title: Comparison of Initial Dual Oral COMbination Therapy to MOnotherapy in Pulmonary Arterial Hypertension With Cardiovascular comorbiDITIES
Pulmonary arterial hypertension (PAH) is a rare, progressive disease associated with poor prognosis, especially in patients with cardiovascular comorbidities. Current guidelines recommend initial combination therapy, but evidence is lacking for patients with significant comorbidities who are often excluded from clinical trials.
The COMMODITIES trial is a multicenter, randomized, controlled study designed to compare the efficacy and safety of initial dual oral combination therapy (tadalafil and ambrisentan) versus oral monotherapy in newly diagnosed PAH patients with at least two cardiovascular comorbidities. The study aims to provide robust evidence to guide treatment strategies in this high-risk population.
Read the detailed description
Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance leading to right heart failure and premature death. Although initial combination therapy with phosphodiesterase-5 inhibitors and endothelin receptor antagonists has demonstrated improved outcomes in patients without major comorbidities, little is known about its benefit-risk balance in patients with cardiovascular comorbidities.
The COMMODITIES study is an investigator-initiated, prospective, randomized, controlled, open-label, phase IV trial conducted under European Regulation (EU) 536/2014. The trial will enroll newly diagnosed PAH patients (confirmed by right heart catheterization) who present with at least two cardiovascular comorbidities (including systemic hypertension, diabetes mellitus, coronary artery disease, obesity, or atrial fibrillation).
Eligible patients will be randomized 1:1 to receive either:
Experimental arm : tadalafil + ambrisentan,
Control arm : : tadalafil +placebo.
The primary endpoint will be the proportion of patients with PAH and cardiovascular comorbidities who achieve after 6 months a low- or an intermediate-low risk profile according to the noninvasive 4-risk strata method as proposed by the 2022 European pulmonary hypertension guidelines.
The total planned sample size is 186, with a study duration of 37 months . Results will provide crucial evidence to inform guideline recommendations and optimize therapeutic strategies in PAH patients with comorbidities.
- Being tested
- Tadalafil, Ambrisentan, Placebo (Ambrisentan-matching)
- Keywords
- PAH, Endothelin Receptor Antagonist (Ambrisentan), Phosphodiesterase-5 Inhibitor (Tadalafil), Cardiovascular Comorbidities, Combination Therapy, Randomized Controlled Trial, Pulmonary arterial hypertension
- Medical subject headings
- Pulmonary Arterial Hypertension, Cardiovascular Diseases
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
TadalafilDrug
Oral phosphodiesterase-5 inhibitor. Initiated at 20 mg once daily for 7 days, then increased to 40 mg once daily (2 × 20 mg tablets). Dose may be reduced to 20 mg once daily if not tolerated.
AmbrisentanDrug
Oral endothelin receptor antagonist. Initiated at 5 mg once daily for 4 weeks, then increased to 10 mg once daily (2 × 5 mg tablets). Dose may be maintained at 5 mg once daily in case of intolerance.
Placebo (Ambrisentan-matching)Drug
Matching placebo for ambrisentan, 2 tablets once daily, identical in appearance to active drug.
| Study group | Role | What they receive |
|---|---|---|
| Tadalafil + Ambrisentan | Experimental | Tadalafil - 20 mg once daily for 7 days, then 40 mg once daily (2 × 20 mg tablets). Dose may be reduced to 20 mg once daily if not tolerated.
Ambrisentan - 5 mg once daily for 4 weeks, then 10 mg once daily (2 × 5 mg tablets). Dose may be maintained at 5 mg once daily in case of intolerance Receives: Drug: Tadalafil; Drug: Ambrisentan |
| Tadalafil + Placebo | Active comparator | Tadalafil - 20 mg once daily for 7 days, then 40 mg once daily (2 × 20 mg tablets). Dose may be reduced to 20 mg once daily if not tolerated.
Placebo - Matching placebo for ambrisentan, 2 tablets once daily. Receives: Drug: Tadalafil; Drug: Placebo (Ambrisentan-matching) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Mesurement of the risk profile according to the non-invasive 4-risk strata method
Proportion of patients with PAH and with at least two cardiovascular comorbidities who achieve after 24 week a low- or an intermediate-low risk profile according to the non-invasive 4-risk strata method as proposed by the 2022 european pulmonary hypertension guidelines.
Measured: Week 24
Secondary outcomes (9)
Pulmonary vascular resistance
Change from baseline to Week 24 in pulmonary vascular resistance, assessed by right heart catheterization and expressed in Wood units (WU).
Measured: week 24
BNP or NT-proBNP
Percent change from baseline to week 24 in BNP or NT-proBNP
Measured: Week 24
6-Minute Walk Distance (6-MWD)
Change from baseline to week 24 in 6-MWD
Measured: Week 24
WHO/NYHA Functional class
Proportion of participants who improve in WHO/NYHA FC at the end of the DBPC Treatment period
Measured: Week 24
TAPSE/systolic pulmonary artery pressure (SPAP) ratio
Change from baseline to week 24 in the TAPSE/systolic pulmonary artery pressure (SPAP) ratio
Measured: Week 24
Death or Nonfatal Clinical Worsening
Rate of Death or Nonfatal Clinical Worsening defined by hospitalisation for PAH worsening or disease progression defined by worsening of functional class and decrease in 6-min walk distance of more than 15% from baseline, or need for additional specific therapy or lung transplantation
Measured: Week 24
emPHasis-10 score
Change from baseline to week 24 in the emPHasis-10 score
Measured: Week 24
EuroQoL-5 dimensions scale 5 levels (EQ-5D-5L)
Change from baseline to week 24 EuroQoL-5 dimensions scale 5 levels (EQ-5D-5L)
Measured: Week 24
Death
All causes of death
Measured: Week 24
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted24 Nov 2025
- Study start28 Apr 2026
- Primary completion14 Feb 2029 (estimated)
- Study completion14 Feb 2029 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Pulmonary Arterial Hypertension (PAH)Studies of the same condition, open and under way.
- More trials run by Assistance Publique - Hôpitaux de ParisThe 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- Participants will be randomized in a 1:1 ratio to receive either tadalafil plus ambrisentan or tadalafil plus placebo, in a parallel assignment design with two treatment arms under double-blind masking.
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 186 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Assistance Publique - Hôpitaux de Paris
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT07245680
- Sponsor's protocol ID
- APHP230847
- Other IDs
- 2023-509891-40-00, 2023
- Acronym
- COMMODITIES
- Status last verified
- May 2026
- First submitted
- 22 Sep 2025
- Last updated
- 13 May 2026
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Study at a glance
From the registry record, last updated by the sponsor on 13 May 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Comparison of Initial Dual Oral COMbination Therapy to MOnotherapy in Pulmonary Arterial Hypertension With Cardiovascular comorbiDITIES
- ClinicalTrials.gov ID
- NCT07245680
- Acronym / sponsor ID
- COMMODITIES / APHP230847
- Keywords
- PAH, Endothelin Receptor Antagonist (Ambrisentan), Phosphodiesterase-5 Inhibitor (Tadalafil), Cardiovascular Comorbidities, Combination Therapy, Randomized Controlled Trial, Pulmonary arterial hypertension
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 186 participants (estimated)
- Lead sponsor
- Assistance Publique - Hôpitaux de ParisUniversity, hospital or other
- Study start
- 28 Apr 2026 (actual)
- Primary completion
- 14 Feb 2029 (estimated)
- Study completion
- 14 Feb 2029 (estimated)
- First posted
- 24 Nov 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.
Pulmonary arterial hypertension (PAH) is a rare, progressive disease associated with poor prognosis, especially in patients with cardiovascular comorbidities. Current guidelines recommend initial combination therapy, but evidence is lacking for patients with significant comorbidities who are often excluded from clinical trials.
The COMMODITIES trial is a multicenter, randomized, controlled study designed to compare the efficacy and safety of initial dual oral combination therapy (tadalafil and ambrisentan) versus oral monotherapy in newly diagnosed PAH patients with at least two cardiovascular comorbidities. The study aims to provide robust evidence to guide treatment strategies in this high-risk population.
Detailed description
Pulmonary arterial hypertension (PAH) is characterized by increased pulmonary vascular resistance leading to right heart failure and premature death. Although initial combination therapy with phosphodiesterase-5 inhibitors and endothelin receptor antagonists has demonstrated improved outcomes in patients without major comorbidities, little is known about its benefit-risk balance in patients with cardiovascular comorbidities.
The COMMODITIES study is an investigator-initiated, prospective, randomized, controlled, open-label, phase IV trial conducted under European Regulation (EU) 536/2014. The trial will enroll newly diagnosed PAH patients (confirmed by right heart catheterization) who present with at least two cardiovascular comorbidities (including systemic hypertension, diabetes mellitus, coronary artery disease, obesity, or atrial fibrillation).
Eligible patients will be randomized 1:1 to receive either:
Experimental arm : tadalafil + ambrisentan,
Control arm : : tadalafil +placebo.
The primary endpoint will be the proportion of patients with PAH and cardiovascular comorbidities who achieve after 6 months a low- or an intermediate-low risk profile according to the noninvasive 4-risk strata method as proposed by the 2022 European pulmonary hypertension guidelines.
The total planned sample size is 186, with a study duration of 37 months . Results will provide crucial evidence to inform guideline recommendations and optimize therapeutic strategies in PAH patients with comorbidities.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 2
- Model description
- Participants will be randomized in a 1:1 ratio to receive either tadalafil plus ambrisentan or tadalafil plus placebo, in a parallel assignment design with two treatment arms under double-blind masking.
| Arm | Type | Receives |
|---|---|---|
| Tadalafil + Ambrisentan | Experimental | Drug: Tadalafil, Drug: AmbrisentanTadalafil - 20 mg once daily for 7 days, then 40 mg once daily (2 × 20 mg tablets). Dose may be reduced to 20 mg once daily if not tolerated. Ambrisentan - 5 mg once daily for 4 weeks, then 10 mg once daily (2 × 5 mg tablets). Dose may be maintained at 5 mg once daily in case of intolerance |
| Tadalafil + Placebo | Active comparator | Drug: Tadalafil, Drug: Placebo (Ambrisentan-matching)Tadalafil - 20 mg once daily for 7 days, then 40 mg once daily (2 × 20 mg tablets). Dose may be reduced to 20 mg once daily if not tolerated. Placebo - Matching placebo for ambrisentan, 2 tablets once daily. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (16 listed)
- Initial PAH diagnosis < 6 months preceding randomisation
- mPAP≥25 mmHg and
- PAWP<15 mmHg and
- with PVR≥3 WU
- History of essential hypertension
Key exclusion criteria (16 listed)
- Porto-pulmonary hypertension
- Uncorrected systemic-to-pulmonary congenital shunt
- Evidence of thromboembolic disease assessed by ventilation perfusion (V/Q) lung scan or CT pulmonary angiography
- Patients listed for lung or heart-lung transplantation at time of screening
- Patients on any PAH-specific drug therapy at any time preceding randomisation
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 |
|---|---|---|
| TadalafilOral phosphodiesterase-5 inhibitor. Initiated at 20 mg once daily for 7 days, then increased to 40 mg once daily (2 × 20 mg tablets). Dose may be reduced to 20 mg once daily if not tolerated. | Drug | Tadalafil + Ambrisentan, Tadalafil + Placebo |
| AmbrisentanOral endothelin receptor antagonist. Initiated at 5 mg once daily for 4 weeks, then increased to 10 mg once daily (2 × 5 mg tablets). Dose may be maintained at 5 mg once daily in case of intolerance. | Drug | Tadalafil + Ambrisentan |
| Placebo (Ambrisentan-matching)Matching placebo for ambrisentan, 2 tablets once daily, identical in appearance to active drug. | Drug | Tadalafil + Placebo |
Primary outcome
Mesurement of the risk profile according to the non-invasive 4-risk strata method
Time frame: Week 24
Proportion of patients with PAH and with at least two cardiovascular comorbidities who achieve after 24 week a low- or an intermediate-low risk profile according to the non-invasive 4-risk strata method as proposed by the 2022 european pulmonary hypertension guidelines.
9 secondary outcomes
Pulmonary vascular resistance
Time frame: week 24
BNP or NT-proBNP
Time frame: Week 24
6-Minute Walk Distance (6-MWD)
Time frame: Week 24
WHO/NYHA Functional class
Time frame: Week 24
TAPSE/systolic pulmonary artery pressure (SPAP) ratio
Time frame: Week 24
Death or Nonfatal Clinical Worsening
Time frame: Week 24
emPHasis-10 score
Time frame: Week 24
EuroQoL-5 dimensions scale 5 levels (EQ-5D-5L)
Time frame: Week 24
Death
Time frame: Week 24
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 13 May 2026.
- Individual participant dataSharing planned: Undecided
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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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Tadalafil and Ambrisentan in people with Pulmonary Arterial Hypertension (PAH) and Comorbidities, run by Assistance Publique - Hôpitaux de Paris at 1 site in France.
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 16 inclusion and 16 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: looking for participants now, as of the sponsor's last update on 13 May 2026. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in France. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
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 Laurent SAVALE,, MD, PhD (+33 1 45 21 79 08, laurent.savale@aphp.fr), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Mesurement of the risk profile according to the non-invasive 4-risk strata method (time frame: Week 24). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 13 May 2026.