Evidence map›Paper›PMID 39407331›Full record

ArticleTrials2024

StratosPHere 2: study protocol for a response-adaptive randomised placebo-controlled phase II trial to evaluate hydroxychloroquine and phenylbutyrate in pulmonary arterial hypertension caused by mutations in BMPR2.

Nina Deliu, Rajenki Das, Angelique May, Joseph Newman, Jo Steele, Melissa Duckworth, Rowena J Jones, Martin R Wilkins, Mark R Toshner, Sofia S Villar

Abstract readClinical Trial Protocol
PubMed Full text at PMC Publisher
In one paragraph

Article in Trials, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 7 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
7citing papers in PubMed, 1 pooled it
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

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

7 citing papers in PubMed, 1 synthesis or guideline pooled it.

  1. Pooled it
  2. Review
  3. Article
  4. Current Evidence on the Potential Role of EndothelialReviews in cardiovascular medicine · 2026
    Review
  5. Nutrients · 2025
    Article
  6. Article
  7. Article
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

10 authors.

Nina DeliuMRC Biostatistics Unit, Cambridge University, Cambridge, UK. nina.deliu@uniroma1.it.ORCID http://orcid.org/0000-0003-2501-8795
Rajenki DasMRC Biostatistics Unit, Cambridge University, Cambridge, UK.
Angelique MayVPD-HLRI, Department of Medicine, University of Cambridge, Cambridge, UK.
Joseph NewmanVPD-HLRI, Department of Medicine, University of Cambridge, Cambridge, UK.
Jo SteelePapworth Trials Unit Collaboration, Royal Papworth Hospital, Cambridge, UK.
Melissa DuckworthPapworth Trials Unit Collaboration, Royal Papworth Hospital, Cambridge, UK.
Rowena J JonesVPD-HLRI, Department of Medicine, University of Cambridge, Cambridge, UK.
Martin R WilkinsImperial College London, Heart Lung Research Institute, London, UK.
Mark R ToshnerVPD-HLRI, Department of Medicine, University of Cambridge, Cambridge, UK.
Sofia S VillarMRC Biostatistics Unit, Cambridge University, Cambridge, UK.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundPulmonary arterial hypertension is a life-threatening progressive disorder characterised by high blood pressure (hypertension) in the arteries of the lungs (pulmonary artery). Although treatable, there is no known cure for this rare disorder, and its exact cause is unknown. Mutations in the bone morphogenetic protein receptor type-2 (BMPR2) are the most common genetic cause of familial pulmonary arterial hypertension. This study represents the first-ever trial of treatments aimed at directly rescuing the BMPR2 pathway, repurposing two drugs that have shown promise at restoring levels of BMPR2 signalling: hydroxychloroquine and phenylbutyrate.

methodsThis three-armed phase II precision medicine study will investigate BMPR2 target engagement and explore the efficacy of two repurposed therapies in pulmonary arterial hypertension patients with BMPR2 mutations. Patients will be stratified based on two BMPR2 mutation classes: missense and haploinsufficient mutations. Eligible subjects will be randomised to one of the three arms (two active therapy arms and a placebo arm, all plus standard of care) following a Bayesian response-adaptive design implemented independently in each stratum and updated in response to a novel panel of primary biomarkers designed to assess biological modification of the disease. DISCUSSION: The results of this trial will provide the first randomised evidence of the efficacy of these therapies to rescue BMPR2 function and will efficiently explore the potential for a differential response of these therapies per mutation class to address causes rather than consequences of this rare disease.

trial registrationThe study has been registered with ISRCTN (ISRCTN10304915, 22/09/2023).

Indexed as

Bone Morphogenetic Protein Receptors, Type IIClinical Trials, Phase II as TopicHydroxychloroquineMutationPhenylbutyratesRandomized Controlled Trials as TopicDrug RepositioningFamilial Primary Pulmonary HypertensionFemaleHumansMaleMulticenter Studies as TopicPrecision MedicinePulmonary Arterial HypertensionTreatment OutcomeBMPR2 protein, humanBone Morphogenetic Protein Receptors, Type IIHydroxychloroquinePhenylbutyratesAdaptive designBayesian response-adaptive randomisationBMPR2 mutationsPhase II trialPrecision medicinePulmonary arterial hypertension

Identifiers

PMID39407331
PMCPMC11475842

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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 OpenQuestion graph.