ArticlePulmonary circulation2022
A trial design to maximize knowledge of the effects of rodatristat ethyl in the treatment of pulmonary arterial hypertension (ELEVATE 2).
Article in Pulmonary circulation, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04712669 (A Phase 2, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Rodatristat Ethyl in Patients With Pulmonary Arterial Hypertension), which is not on this map. Cited by 19 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
A Phase 2, Dose-Ranging, Randomized, Double-Blind, Placebo-Controlled, Multicenter Study of Rodatristat Ethyl in Patients With Pulmonary Arterial Hypertension
Who cites it
19 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- A Systematic Review of Novel Therapies of Pulmonary Arterial Hypertension.American journal of cardiovascular drugs : drugs, devices, and other interventions · 2024Pooled it
- Mechanism and Treatment of Right Ventricular Failure Due to Pulmonary Hypertension in Children.Children (Basel, Switzerland) · 2025Review
- New therapies in pulmonary arterial hypertension: Recent insights.International journal of cardiology. Congenital heart disease · 2025Article
- Mechanisms and treatment of pulmonary arterial hypertension.Nature reviews. Cardiology · 2025Review
- Aromatic Amino Acid Hydroxylases as Off-Targets of Histone Deacetylase Inhibitors.ACS chemical neuroscience · 2024Article
- Current Overview of the Biology and Pharmacology in Sugen/Hypoxia-Induced Pulmonary Hypertension in Rats.Journal of aerosol medicine and pulmonary drug delivery · 2024Review
- Novel Tryptophan Hydroxylase Inhibitor TPT-001 Reverses PAH, Vascular Remodeling, and Proliferative-Proinflammatory Gene Expression.JACC. Basic to translational science · 2024Article
- Recent developments in connective tissue disease associated pulmonary arterial hypertension.International journal of cardiology. Congenital heart disease · 2024Review
- TPT-004, a Next-Generation Inhibitor of Tryptophan Hydroxylase, Ameliorates Pulmonary Arterial Hypertension in Rats.Journal of the American Heart Association · 2024Article
- Future Perspectives of Pulmonary Arterial Hypertension: A Review of Novel Pipeline Treatments and Indications.Drugs in R&D · 2024Review
- 5-HTP inhibits eosinophilia via intracellular endothelial 5-HTRs; SNPs in 5-HTRs associate with asthmatic lung function.Frontiers in allergy · 2024Article
- Current Management and Future Directions for Pulmonary Arterial Hypertension Associated with Congenital Heart Disease.Journal of personalized medicine · 2023Review
- A Review of Serotonin in the Developing Lung and Neonatal Pulmonary Hypertension.Biomedicines · 2023Review
- Recent Advances in the Treatment of Pulmonary Arterial Hypertension Associated with Connective Tissue Diseases.Pharmaceuticals (Basel, Switzerland) · 2023Review
- Article
- New Drugs and Therapies in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2023Review
- The Evolving Management and Treatment Options for Patients with Pulmonary Hypertension: Current Evidence and Challenges.Vascular health and risk management · 2023Review
- Strategizing Drug Therapies in Pulmonary Hypertension for Improved Outcomes.Pharmaceuticals (Basel, Switzerland) · 2022Review
- A trial design to maximize knowledge of the effects of rodatristat ethyl in the treatment of pulmonary arterial hypertension (ELEVATE 2).Pulmonary circulation · 2022Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Serotonin plays a key role in the development and maintenance of the pathobiology associated with pulmonary arterial hypertension (PAH). Platelet-driven and locally produced serotonin from lung tissue and arterial endothelial cells induce excessive growth of pulmonary artery smooth muscle cells. The unchecked growth of these cells is a major driver of PAH including the remodeling of pulmonary arteries that dramatically reduces the diameter and flexibility of the arterial lumen. Tryptophan hydroxylase 1 (TPH1) is the rate-limiting enzyme for biosynthesis of serotonin and is upregulated in PAH arterial endothelial cells, supporting TPH1 inhibition to treat PAH. Targeting the serotonin pathway via inhibition of peripheral serotonin and local production in diseased tissues, rather than individual receptor-mediated or receptor-independent mechanisms, may result in the ability to halt or reverse pulmonary vascular remodeling. Rodatristat ethyl, a prodrug for rodatristat, a potent, peripheral inhibitor of TPH1, has demonstrated efficacy in monocrotaline and SUGEN hypoxia nonclinical models of PAH and robust dose-dependent reductions of 5-hydroxyindoleacetic acid, the major metabolite of serotonin in plasma and urine of healthy human subjects. ELEVATE 2 (NCT04712669) is a Phase 2b, double-blind, multicenter trial where patients with PAH are randomized to placebo, 300 or 600 mg twice daily of rodatristat ethyl. The trial incorporates endpoints to generate essential clinical efficacy, safety, pharmacokinetic, and pharmacodynamic data needed to evaluate the ability of rodatristat ethyl to ameliorate PAH by halting or reversing pulmonary vascular remodeling through its unique mechanism of TPH1 inhibition. Herein we describe the experimental design highlighting the trial's unique features.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.