Evidence mapPaperPMID 41849831Full record

Trial reportEBioMedicine2026

Harnessing metabolomics and proteomics in a clinical trial for pulmonary arterial hypertension: insights from post-hoc analysis of the REHAB-PH trial.

Hongyang Pi, Lu Xia, Samuel G Rayner, Jeffrey L Probstfield, Kelley R Branch, Ali Shojaie, Peter J Leary, Sina A Gharib

Abstract readRandomized Controlled Trial
In one paragraph

Trial report in EBioMedicine, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from 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.

2 · The registry

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.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors.

Hongyang PiDivision of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA, USA.
Lu XiaDepartment of Statistics and Probability, Michigan State University, USA.
Samuel G RaynerDivision of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA, USA.
Jeffrey L ProbstfieldDivision of Cardiology, University of Washington, Seattle, WA, USA.
Kelley R BranchDivision of Cardiology, University of Washington, Seattle, WA, USA.
Ali ShojaieDepartment of Statistics, University of Washington, USA; Department of Biostatistics, University of Washington, USA.
Peter J LearyDivision of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA, USA; Department of Epidemiology, University of Washington, USA. Electronic address: learyp@uw.edu.
Sina A GharibDivision of Pulmonary, Critical Care and Sleep Medicine, University of Washington, Seattle, WA, USA.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundThe significant clinical and molecular heterogeneity of pulmonary arterial hypertension (PAH) poses challenges in identifying effective therapies. Advanced multidimensional profiling offers an opportunity to capture molecular responses and assess biomarker stability, yet its application in randomised trials remains limited.

methodsWe evaluated the multi-omic profiles of participants with PAH in a randomised, placebo-controlled trial of famotidine. Plasma metabolomic and proteomic profiling was performed at enrolment and 24 weeks. Baseline profiles were compared between treatment arms to assess randomisation balance. Intraclass correlation coefficients quantified within-subject stability over time. Linear regression models adjusting for age, sex, body mass index and PAH aetiology evaluated famotidine's molecular effects. False discovery rate was controlled for multiple comparisons.

findingsFor the 79 participants, baseline multi-omic profiles were similar between groups. At 24 weeks, 34 and 37 participants remained in the famotidine and placebo groups respectively. The placebo group showed high molecular stability, while greater variability was observed in the famotidine group. Famotidine treatment was associated with significant changes across 191 proteomic pathways (q-value <0.05), but no metabolomic changes remained significant after multiple-testing correction.

interpretationIntegrating multi-omics into a prospective clinical trial is feasible and yields stable longitudinal profiles in the absence of intervention. While famotidine did not yield clinical benefit, associated proteomic changes illustrate how molecular profiling can reveal treatment-related biology and inform future trial design. These findings highlight the broader utility of multi-omics for evaluating drug responses and identifying molecular endotypes in PAH and beyond.

fundingUS National Institutes of Health.

Indexed as

Hypertension, PulmonaryMetabolomicsProteomicsAdultBiomarkersFamotidineFemaleHumansMaleMetabolomeMiddle AgedMultiomicsTreatment OutcomeBiomarkersFamotidineClinical trialLongitudinal studyMetabolomicsProteomicsPulmonary arterial hypertension

Identifiers

PMID41849831
PMCPMC13014658

What Socratic holds

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Registered trials

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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 Socratic graph.