PAH Therapies for Pulmonary Arterial Hypertension

(CARE PAH Trial)

No longer recruiting at 106 trial locations

Overseen By Study Contact

Age: 18+

Sex: Any

Trial Phase: Phase 4

Sponsor: Actelion

Must be taking: PAH therapies, Macitentan

Disqualifiers: Interventional trial, Obstructive lung disease, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Prior Safety Data This treatment has passed at least one previous human trial

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 6 years

What You Need to Know Before You Apply

What is the purpose of this trial?

This trial focuses on individuals with pulmonary arterial hypertension (PAH), a condition characterized by high blood pressure in the lungs, which strains the heart. Researchers aim to gain insights into the progression of PAH, the treatments used, and the outcomes of these treatments in real-world settings. Participants will either begin a new PAH treatment or continue using macitentan, a specific PAH therapy. Those experiencing PAH symptoms and starting or already on specific therapies may be suitable candidates for this trial. As a Phase 4 trial, the study examines an FDA-approved treatment to assess its benefits for a broader patient population.

Will I have to stop taking my current medications?

The trial does not specify if you need to stop taking your current medications. However, if you are starting a new PAH therapy, it should not have been used within 3 months before the trial starts.

What is the safety track record for PAH therapies?

Studies have shown that treatments for pulmonary arterial hypertension (PAH) are generally safe and well-tolerated. For example, the medication riociguat, already approved for treating PAH, has demonstrated safety. Research on another PAH treatment, treprostinil, found it improved exercise ability without major safety concerns.

These treatments undergo testing in real-world settings, meaning they are used in everyday medical practice, not just in labs. This indicates that doctors have observed their safe use in many patients.

For those considering joining a trial, it's reassuring to know that these therapies have been used safely in others with PAH. Always consult your doctor about what’s best for you. ^{1 2 3 4 5}

Why are researchers enthusiastic about this study treatment?

Researchers are excited about these PAH therapies because they aim to optimize treatment by assessing real-world data from patients who are starting new PAH treatments. Unlike standard treatments like endothelin receptor antagonists, phosphodiesterase-5 inhibitors, or prostacyclin analogs, this approach gathers insights from how these therapies are used in everyday clinical settings, potentially leading to more personalized and effective treatment strategies. By analyzing data from routine clinical use, researchers hope to gain a deeper understanding of how these therapies can be best utilized, which could enhance patient outcomes and guide future treatment guidelines.

What is the effectiveness track record for PAH therapies?

Research has shown that current treatments for pulmonary arterial hypertension (PAH) effectively help patients. Studies have found that medications targeting key bodily processes can significantly improve treatment outcomes for people with PAH. Additionally, combining medications often results in greater improvements than using a single medication. Participants in this trial will begin PAH therapy, either as first-line therapy, replacement therapies, or in combination with other PAH therapies. These treatments can lead to better symptom control and potentially slower disease progression. Overall, evidence supports the effectiveness of these treatments in managing PAH. ^{2 6 7 8 9}

Who Is on the Research Team?

Actelion Clinical Trial

Principal Investigator

Actelion

Are You a Good Fit for This Trial?

Inclusion Criteria

PAH diagnosis confirmed by hemodynamic evaluation at rest at any time prior to or at the index date fulfilling all of the criteria below: a) Mean pulmonary artery pressure greater than (>) 20 millimeters of mercury (mm Hg), and b) Pulmonary artery wedge pressure or left ventricular end diastolic pressure less than or equal to (<=) 15 mm Hg, and c) Pulmonary vascular resistance greater than or equal to (>=) 3 Wood Units (that is, >= 240 dynes seconds per centimeters penta [dyn∙sec/cm^5])

All mandated assessments must be performed and recorded at the baseline visit before the initiation of the new PAH therapy at the index date or enrollment in the study.

Participant satisfies either a or b: a) Newly initiating 1 or more PAH therapy(ies) (as monotherapy or add-on therapy) at index date. These newly initiated PAH therapies should not have been used within 3 months of the index date; b) Taking macitentan 10 milligrams (mg) therapy (as monotherapy or in combination) with no changes in PAH therapy for within 3 months prior to the index date

Exclusion Criteria

Participants enrolled in any interventional clinical trial with an investigational therapy in the 3-month period prior to index date

Currently enrolled in an observational study sponsored or managed by a Janssen company

Presence of moderate or severe obstructive lung disease (forced expiratory volume in 1 second [FEV1] / forced vital capacity [FVC] <70%; and FEV1 <60% of predicted after bronchodilator administration) in participants with a known or suspected history of significant lung disease, as documented by a spirometry test performed within 1 year prior to screening

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Baseline Assessment

Participants undergo baseline assessments to determine clinical characteristics and initiate PAH therapy

1-2 weeks

Treatment

Participants newly initiate PAH therapy and are monitored for disease progression and outcomes

Up to 6 years

Follow-up

Participants are monitored for safety and effectiveness after treatment

6 months

What Are the Treatments Tested in This Trial?

Interventions

• PAH Therapies

How Is the Trial Designed?

Group I: Participants with PAH Experimental Treatment 1 Intervention

Participants with pulmonary arterial hypertension (PAH) who newly initiate any PAH therapy(ies) at the index date (date when a participant starts the first new PAH therapy after baseline assessments) in a routine clinical setting, either as first-line therapy, as replacement therapies, as concomitant with other PAH therapies, or have already been receiving macitentan 10 milligrams (mg) for at least 3 months prior to the index date. The primary data source for this study will be the medical records of each participant.

Who Is Running the Clinical Trial?

Actelion

Lead Sponsor

Trials

192

Recruited

35,500+

Jean-Paul Clozel

Actelion

Chief Executive Officer since 1997

MD from University of Basel

Martine Clozel

Actelion

Chief Medical Officer since 1997

MD from University of Geneva

Published Research Related to This Trial

The recent fatal adverse event in the BIA-102474-101 clinical trial highlights significant limitations in the current safety review process for first-into-human trials, despite previous trials with similar compounds being conducted without incident.

To improve safety in future trials, it is crucial to implement sequential dosing strategies, thorough reviews of preclinical toxicity studies, and systematic risk assessments, especially for novel compounds that may pose higher risks.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Implications of the BIA-102474-101 study for review of first-into-human clinical trials. Eddleston, M., Cohen, AF., Webb, DJ.[2021]

The study found that there is no formal definition of 'adversity' or guidance on determining the No Observed Adverse Effect Level (NOAEL) in safety pharmacology, indicating a lack of standardized practices in this area.

It was concluded that using NOAEL in safety pharmacology is not recommended, as the diverse functional endpoints measured do not fit into a simple toxic/non-toxic classification, suggesting a need for more nuanced risk assessments in drug development.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Is there a role for the no observed adverse effect level in safety pharmacology? Mow, T., Andersen, NK., Dragsted, N., et al.[2021]

In a study of 13 patients with de novo adverse-risk acute myeloid leukemia (AML), the combination of venetoclax, homoharringtonine, and cytarabine (VHA regimen) resulted in a high complete remission rate of 84.6%, with all responders showing no measurable residual disease.

While the VHA regimen was effective, it was associated with significant side effects, including grade 3-4 neutropenia and febrile neutropenia in 30.8% of patients, indicating that while promising, careful monitoring for adverse events is necessary.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Outcomes of venetoclax combined with homoharringtonine and cytarabine in fit adults patients with de novo adverse-risk acute myeloid leukaemia: A single-centre retrospective analysis. Song, BQ., Kong, X., Pu, Y., et al.[2023]

The safety of marketed drugs is a significant concern, as some commonly prescribed medications can lead to serious or life-threatening side effects in patients.

The ChEMBL resource will provide a curated drug safety data set, including toxicity classifications and black box warnings, which will be freely available and regularly updated to aid in drug safety research and discovery.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Drug Safety Data Curation and Modeling in ChEMBL: Boxed Warnings and Withdrawn Drugs. Hunter, FMI., Bento, AP., Bosc, N., et al.[2023]

Citations

1. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC7691927/

Long-term outcomes in pulmonary arterial hypertension by ... The randomized, controlled trial analysis demonstrates that current medical therapies have a beneficial treatment effect in this population.

2. pubmed.ncbi.nlm.nih.gov pubmed.ncbi.nlm.nih.gov/38416633/

Pulmonary arterial hypertension treatment - PubMed - NIH Conclusions: Drugs targeting the three traditional treatment pathways significantly improve outcomes in PAH, with significant treatment ...

3. sciencedirect.com sciencedirect.com/science/article/pii/S2666668525000072

New therapies in pulmonary arterial hypertension: Recent ... This review includes both preclinical and clinical trial data that support efficacy, safety and the future potential of such therapies. Collectively, these ...

4. publications.ersnet.org publications.ersnet.org/content/erj/64/4/2401325

Treatment algorithm for pulmonary arterial hypertension Compared with monotherapy, larger improvements are seen with combination therapy and thus most patients with PAH are candidates for oral or oral plus parenteral ...

5. icer.org icer.org/news-insights/press-releases/icer-publishes-evidence-report-on-treatment-for-pulmonary-arterial-hypertension/

ICER Publishes Evidence Report on Treatment for ... Based on the currently available data, sotatercept added to background therapy appears to improve clinical outcomes for patients with PAH. It has a less ...

6. pmc.ncbi.nlm.nih.gov pmc.ncbi.nlm.nih.gov/articles/PMC8172220/

Efficacy and safety of novel-targeted drugs in the treatment ... To assess the efficacy and safety of PAH therapies, five efficacy outcomes [6-minute walking distance (6MWD), mean pulmonary arterial pressure (mPAP), WHO ...

7. academic.oup.com academic.oup.com/eurheartj/article/45/Supplement_1/ehae666.2238/7836971

safety and efficacy of treprostinil for the treatment of pulmonary ... The addition of Treprostinil therapy for patients with PAH significantly improved exercise capacity, as evidenced by an increase in the 6MWD ...

8. publications.ersnet.org publications.ersnet.org/content/erj/50/suppl61/PA3534

Safety of riociguat for the treatment of pulmonary hypertension Riociguat is approved for the treatment of patients with pulmonary arterial hypertension (PAH) and chronic thromboembolic pulmonary hypertension (CTEPH).

9. nejm.org nejm.org/doi/full/10.1056/NEJMoa2213558

Phase 3 Trial of Sotatercept for Treatment of Pulmonary ... In the phase 3 STELLAR trial, we further investigated the efficacy, safety, and adverse-event profile of sotatercept in combination with stable background ...