AZD3427 for Heart Failure with Pulmonary Hypertension
(Re-PHIRE Trial)
Recruiting in Palo Alto (17 mi)
+63 other locations
Age: 18+
Sex: Any
Travel: May Be Covered
Time Reimbursement: Varies
Trial Phase: Phase 2
Waitlist Available
Sponsor: AstraZeneca
Prior Safety Data
Trial Summary
What is the purpose of this trial?
This study is intended to assess the ability of AZD3427 to reduce pulmonary vascular resistance (PVR) after 24 weeks of treatment in participants with heart failure (HF) and pulmonary hypertension (PH) Group 2
Do I have to stop taking my current medications for this trial?
The trial does not specify if you need to stop taking your current medications. However, participants must be on stable heart failure standard of care medication, including diuretics, to be eligible.
What data supports the idea that AZD3427 for Heart Failure with Pulmonary Hypertension is an effective drug?
The available research does not provide specific data on AZD3427 for Heart Failure with Pulmonary Hypertension. However, it mentions other treatments like pulmonary vasodilators, which are used for similar conditions. In patients with severe pulmonary hypertension due to lung disease, these treatments did not improve walking distance or functional class, but they did reduce a marker in the blood that indicates heart stress. This suggests that while there might be some benefits, the effectiveness of such treatments can vary depending on the specific type of lung disease. Further study is needed to determine if these treatments can slow disease progression.12345
What safety data is available for AZD3427 in heart failure with pulmonary hypertension?
The provided research does not contain any safety data for AZD3427 or its variants (AZD-3427, azd 3427, azd3427) in the context of heart failure with pulmonary hypertension. The studies focus on other treatments like selexipag, sodium nitrite, ambrisentan, and sitaxsentan for pulmonary hypertension.678910
Is the drug AZD3427 a promising treatment for heart failure with pulmonary hypertension?
Eligibility Criteria
Adults over 18 with heart failure and pulmonary hypertension group 2, weighing at least 50 kg, on stable heart medications can join. They must have certain echocardiographic signs of PH and elevated artery pressure from a right heart catheterization. Excluded are those allergic to AZD3427 or similar drugs, who've had it before, with other types of PH, significant health issues, planned major heart procedures or severe lung disease.Inclusion Criteria
I am 18 years old or older.
I am willing and able to sign the consent form.
My heart ultrasound shows I might have pulmonary hypertension.
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Exclusion Criteria
History of hypersensitivity to SC injections or devices
I have been hospitalized for heart failure.
I have previously taken AZD3427.
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Treatment Details
Interventions
- AZD3427 (Other)
Trial OverviewThe trial is testing AZD3427's effectiveness in reducing lung blood vessel resistance after six months compared to a placebo in patients with both heart failure and pulmonary hypertension group 2. Participants will be randomly assigned to receive either the drug or a placebo.
Participant Groups
4Treatment groups
Experimental Treatment
Placebo Group
Group I: AZD3427 Dose CExperimental Treatment1 Intervention
The participants will receive single dose of AZD3427 Dose C every 2 weeks for 24 weeks from Day 1 to Day 155.
Group II: AZD3427 Dose BExperimental Treatment1 Intervention
The participants will receive single dose of AZD3427 Dose B every 2 weeks for 24 weeks from Day 1 to Day 155.
Group III: AZD3427 Dose AExperimental Treatment1 Intervention
The participants will receive single dose of AZD3427 Dose A every 2 weeks for 24 weeks from Day 1 to Day 155.
Group IV: PlaceboPlacebo Group1 Intervention
The participants will receive single dose of placebo every 2 weeks for 24 weeks from Day 1 to Day 155.
Find a Clinic Near You
Research Locations NearbySelect from list below to view details:
Research SiteLos Angeles, CA
Research SiteSaint Louis, MO
Research SiteRock Hill, SC
Research SiteBeverly Hills, CA
More Trial Locations
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Who Is Running the Clinical Trial?
AstraZenecaLead Sponsor
ParexelIndustry Sponsor
References
Severe pulmonary hypertension in lung disease: phenotypes and response to treatment. [2015]Pulmonary hypertension (PH) due to lung disease (World Health Organization (WHO) group 3) is common, but severe PH, arbitrarily defined as mean pulmonary artery pressure ≥35 mmHg is reported in only a small proportion. Whether these should be treated as patients in WHO group 1 (i.e. pulmonary arterial hypertension) with PH-targeted therapies is unknown. We compared the phenotypic characteristics and outcomes of 118 incident patients with severe PH and lung disease with 74 idiopathic pulmonary arterial hypertension (IPAH) patients, all treated with pulmonary vasodilators. Lung disease patients were older, more hypoxaemic, and had lower gas transfer, worse New York Heart Association functional class and lower 6-min walking distance (6MWD) than IPAH patients. Poorer survival in those with lung disease was driven by the interstitial lung disease (ILD) cohort. In contrast to IPAH, where significant improvements in 6MWD and N-terminal pro-brain natruiretic peptide (NT-proBNP) occurred, PH therapy in severe PH lung disease did not lead to improvement in 6MWD or functional class, but neither was deterioration seen. NT-proBNP decreased from 2200 to 1596 pg·mL(-1) (p=0.015). Response varied by lung disease phenotype, with poorer outcomes in patients with ILD and emphysema with preserved forced expiratory volume in 1 s. Further study is required to investigate whether vasodilator therapy may delay disease progression in severe PH with lung disease.
Ambrisentan therapy for pulmonary arterial hypertension. [2023]The purpose of this study was to examine the efficacy and safety of four doses of ambrisentan, an oral endothelin type A receptor-selective antagonist, in patients with pulmonary arterial hypertension (PAH).
Levosimendan Improves Hemodynamics and Exercise Tolerance in PH-HFpEF: Results of the Randomized Placebo-Controlled HELP Trial. [2022]The purpose of this study was to evaluate the effects of intravenous levosimendan on hemodynamics and 6-min walk distance (6MWD) in patients with pulmonary hypertension and heart failure with preserved ejection fraction (PH-HFpEF).
Selective pulmonary vasodilatory effect of ZSY-27 in dogs with pulmonary hypertension due to pulmonary embolism. [2019]The pulmonary vasodilator effect of ZSY-27, a newly synthesized phosphodiesterase inhibitor, was studied in dogs with pulmonary hypertension resulting from autologous muscle-induced pulmonary embolism (PE). A bolus injection of ZSY-27 (1 mg/kg) significantly decreased mean pulmonary arterial pressure from 32 +/- 4 to 24 +/- 5 mm Hg and pulmonary vascular resistance index from 415 +/- 60 to 316 +/- 94 dyne.sec/cm5.m2. ZSY-27 did not change mean arterial pressure. The cardiac index was slightly increased and the systemic vascular resistance index was slightly decreased after ZSY-27 injection, but these changes were not statistically significant. This study suggests that ZSY-27 is a possible therapeutic agent for pulmonary hypertension secondary to PE.
[Efficacy and safety of ambrisentan therapy in Chinese patients with pulmonary hypertension]. [2016]To explore the efficacy, safety and tolerance of ambrisentan, a high-selective endothelin receptor antagonist, in Chinese patients with pulmonary hypertension (PH).
Selexipag for the treatment of children with pulmonary arterial hypertension: First multicenter experience in drug safety and efficacy. [2021]The European Pediatric Pulmonary Vascular Disease Network (EPPVDN) investigated the safety and efficacy of add-on selexipag, an oral prostacyclin receptor agonist approved for pulmonary arterial hypertension (PAH) in adults, in the largest, exploratory pediatric cohort to date.
Real-world practice patterns and characteristics of adverse events with selexipag in Korean patients with pulmonary arterial hypertension. [2022]Optimizing an individual dose with careful management of adverse events (AEs) is essential in the treatment with selexipag approved for pulmonary arterial hypertension (PAH). This study aims to identify real-world practice patterns and AE characteristics of selexipag.
Acute hemodynamic effects of inhaled sodium nitrite in pulmonary hypertension associated with heart failure with preserved ejection fraction. [2023]Pulmonary hypertension (PH) is associated with poor outcomes, yet specific treatments only exist for a small subset of patients. The most common form of PH is that associated with left heart disease (Group 2), for which there is no approved therapy. Nitrite has shown efficacy in preclinical animal models of Group 1 and 2 PH, as well as in patients with left heart failure with preserved ejection fraction (HFpEF). We evaluated the safety and efficacy of a potentially novel inhaled formulation of nitrite in PH-HFpEF patients as compared with Group 1 and 3 PH.
Evaluation of efficacy, safety and tolerability of Ambrisentan in Chinese adults with pulmonary arterial hypertension: a prospective open label cohort study. [2018]Although several new drugs have been approved in recent years, pulmonary arterial hypertension (PAH) remains a rapidly progressive disease with a poor prognosis. Ambrisentan, a selective endothelin type A antagonist, has been approved for treatment of PAH. This open label study assessed the efficacy and safety of ambrisentan in Chinese subjects with PAH.
Sitaxsentan for the treatment of pulmonary arterial hypertension: a 1-year, prospective, open-label observation of outcome and survival. [2021]Despite advances in the management of pulmonary arterial hypertension (PAH), the mortality rate remains excessive. Long-term efficacy evaluations are needed to guide therapeutic management. The purpose of this study is to present 1-year observational data with two endothelin antagonists, sitaxsentan and bosentan, in a prospective, open-label study.
Pulmonary vasodilation in acute and chronic heart failure: empiricism and evidence. [2021]Pulmonary hypertension in heart failure is associated with exercise intolerance and adverse outcomes. With the availability of multiple drugs that cause pulmonary vasodilation and decrease pulmonary arterial pressure, pulmonary hypertension becomes an attractive therapeutic target. Out of several classes of medications, oral phosphodiesterase inhibitors emerge as the most promising in terms of symptomatic improvement, hemodynamic benefits, reverse cardiac remodeling, and functional capacity. Future trials will show whether the use of these drugs translates to decreased morbidity and mortality in heart failure.
Upfront triple combination therapy in pulmonary arterial hypertension: a pilot study. [2018]Patients with severe pulmonary arterial hypertension (PAH) in New York Heart Association (NYHA) functional class (FC) III/IV have a poor prognosis, despite survival benefits being demonstrated with intravenous epoprostenol. In this pilot study, the efficacy and safety of a triple combination therapy regimen in patients with severe PAH was investigated. Data from newly diagnosed NYHA FC III/IV PAH patients (n=19) initiated on upfront triple combination therapy (intravenous epoprostenol, bosentan and sildenafil) were collected retrospectively from a prospective registry. Significant improvements in 6-min walk distance and haemodynamics were observed after 4 months' triple combination therapy in 18 patients (p
Combination Therapy of Pulmonary Arterial Hypertension with Vardenafil and Macitentan Assessed in a Human Ex Vivo Model. [2020]Treatment of pulmonary arterial hypertension (PAH) by vasodilator drug monotherapy is often limited in its effectiveness. Combination therapy may help to improve treatment and to reduce drug toxicity. This study assessed the combination of the endothelin receptor antagonist macitentan and the phosphodiesterase-5 inhibitor vardenafil in a human ex vivo model.
The pulmonary physician in critical care. 13: the pulmonary circulation and right ventricular failure in the ITU. [2020]The management of severe pulmonary hypertension associated with right ventricular failure is reviewed and its relevance to adults with acute respiratory distress syndrome (ARDS) is discussed.