Trial reportThe European respiratory journal2024
MK-5475, an inhaled soluble guanylate cyclase stimulator, for treatment of pulmonary arterial hypertension: the INSIGNIA-PAH study.
Trial report in The European respiratory journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT04732221 (A Phase 2/3, Multicenter, Randomized, Double-blind, Placebo-Controlled, Adaptive Design Study to Evaluate the Efficacy and Safety of MK-5475 in Adults With Pulmonary Arterial Hypertension), which is not on this map. Cited by 8 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.
A Phase 2/3, Multicenter, Randomized, Double-blind, Placebo-Controlled, Adaptive Design Study to Evaluate the Efficacy and Safety of MK-5475 in Adults With Pulmonary Arterial Hypertension
Who cites it
8 citing papers in PubMed, 1 synthesis or guideline pooled it.
- 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
- Inhaled pulmonary vasodilators in pulmonary hypertension: Perioperative use and clinical considerations.JHLT open · 2026Article
- Beyond Vasodilation: Sotatercept and the Dawn of Disease Modification in Connective Tissue Disease-Associated Pulmonary Arterial Hypertension.International journal of rheumatic diseases · 2026Article
- Pulmonary arterial hypertension from a translational perspective: Bridging pathophysiology and treatment.Chinese medical journal · 2026Review
- Pulmonary hypertension associated with interstitial lung disease: a state-of-the-art review.The European respiratory journal · 2026Review
- Update on pulmonary hypertension.Respiratory research · 2026Review
- Article
- Long-term safety and tolerability of frespaciguat: the INSIGNIA-PAH extension.The European respiratory journal · 2026Article
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMK-5475 is an investigational inhaled soluble guanylate cyclase stimulator hypothesised to avoid most side-effects of systemic vasodilation.
methodsThe phase 2 INSIGNIA-PAH (NCT04732221) trial randomised adults with pulmonary arterial hypertension (PAH) on stable background therapy 1:1:1:1 to once-daily dosing with placebo, MK-5475 32 µg, 100 µg or 380 µg
objectivesThe objectives were to evaluate pulmonary vascular resistance (PVR; primary), 6-min walk distance (6MWD; secondary), additional selected haemodynamic parameters, and safety and tolerability in participants with PAH.
results168 participants were randomised to placebo (n=41), MK-5475 32 µg (n=42), 100 µg (n=44), and 380 µg (n=41). Median age was 51 years. Most participants were female (73.8%), diagnosed with idiopathic PAH (63.7%), receiving concomitant phosphodiesterase type 5 inhibitors (PDE5i; 93.5%), and treated with double or triple combination therapy (85.1%). At week 12, the placebo-corrected changes in PVR by least-squares means were -9.2% (95% CI -21.3%, 2.9%; p=0.068) with 32 µg, -22.0% (95% CI -33.7%, -10.3%; p<0.001) with 100 µg, and -19.9% (95% CI -33.4%, -6.4%; p=0.002) with 380 µg MK-5475. No treatment differences
conclusionsIn participants with PAH on stable background therapy, including PDE5i, inhaled MK-5475 reduced PVR and was well tolerated, without evidence of systemic side-effects such as hypotension, suggesting a pulmonary selective pharmacodynamic effect.
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