ArticlePulmonary circulation2022
An open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of GSK2586881 in participants with pulmonary arterial hypertension.
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 NCT03177603 (An Open-label, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Doses of GSK2586881 in Participants With Pulmonary Arterial Hypertension), which is not on this map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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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.
An Open-label, Dose-escalation Study to Evaluate the Safety, Tolerability, Pharmacokinetics and Pharmacodynamics of Single Doses of GSK2586881 in Participants With Pulmonary Arterial Hypertension
Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it, 15 citations in OpenAlex.
- Management of pulmonary arterial hypertension in systemic sclerosis: from classical treatments to new horizons.European respiratory review : an official journal of the European Respiratory Society · 2026Pooled it
- Developmental Progress and Future Potential for Inhaled Biologics in the Treatment of Respiratory Diseases.Drugs · 2026Review
- Therapeutic Opportunities Targeting the ACE2/Ang-(1-7)/MasR Pathway in Cardiometabolic Disease.Current hypertension reports · 2026Review
- Fenofibrate as a Modulator of the Renin-Angiotensin System in Su/Hx-Induced Pulmonary Arterial Hypertension.International journal of molecular sciences · 2025Article
- Pulmonary Hypertension Associated with Interstitial Lung Disease (PH-ILD): Back to the Future.Advances in therapy · 2025Review
- Novel Antihypertensive Medications to Target the Renin-Angiotensin System: Mechanisms and Research.Reviews in cardiovascular medicine · 2025Review
- Modulation of the pharmacokinetics of soluble ACE2 decoy receptors through glycosylation.Molecular therapy. Methods & clinical development · 2024Article
- Angiotensin-Converting Enzyme 2 (ACE2) Signaling in Pulmonary Arterial Hypertension: Underpinning Mechanisms and Potential Targeting Strategies.International journal of molecular sciences · 2023Article
- New Drugs and Therapies in Pulmonary Arterial Hypertension.International journal of molecular sciences · 2023Review
- A novel ACE2 decoy for both neutralization of SARS-CoV-2 variants and killing of infected cells.Frontiers in immunology · 2023Article
- Pathogenic Mechanisms of Pulmonary Arterial Hypertension: Homeostasis Imbalance of Endothelium-Derived Relaxing and Contracting Factors.JACC. Asia · 2022Review
- An open-label, dose-escalation study to evaluate the safety, tolerability, pharmacokinetics, and pharmacodynamics of single doses of GSK2586881 in participants with pulmonary arterial hypertension.Pulmonary circulation · 2022Article
Corrections and comments
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Authors and funding
17 authors at 10 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Preclinical and early clinical studies suggest that angiotensin-converting enzyme type 2 activity may be impaired in patients with pulmonary arterial hypertension (PAH); therefore, administration of exogenous angiotensin-converting enzyme type 2 (ACE2) may be beneficial. This Phase IIa, multi-center, open-label, exploratory, single-dose, dose-escalation study (NCT03177603) assessed the potential vasodilatory effects of single doses of GSK2586881 (a recombinant human ACE2) on acute cardiopulmonary hemodynamics in hemodynamically stable adults with documented PAH who were receiving background PAH therapy. Successive cohorts of participants were administered a single intravenous dose of GSK2586881 of 0.1, 0.2, 0.4, or 0.8 mg/kg. Dose escalation occurred after four or more participants per cohort were dosed and a review of safety, tolerability, pharmacokinetics, and hemodynamic data up to 24 h postdose was undertaken. The primary endpoint was a change in cardiopulmonary hemodynamics (pulmonary vascular resistance, cardiac index, and mean pulmonary artery pressure) from baseline. Secondary/exploratory objectives included safety and tolerability, effect on renin-angiotensin system peptides, and pharmacokinetics. GSK2586881 demonstrated no consistent or sustained effect on acute cardiopulmonary hemodynamics in participants with PAH receiving background PAH therapy (
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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.