Evidence map›Paper›PMID 41316297›Full record

Trial reportRespiratory research2025

A composite endpoint for systemic sclerosis-associated interstitial lung disease: association with mortality in two clinical trial cohorts.

Elizabeth R Volkmann, Holly Wilhalme, Sam Good, Grace Hyun J Kim, Jonathan Goldin, Michael D Roth, Donald P Tashkin

2 registry-linked trialsAbstract readClinical Trial, Phase IIClinical Trial, Phase IIIMulticenter Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Respiratory research, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to 2 registered trials, which are not on this map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–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.

NCT00004563 phase3completednot on this map

Cyclophosphamide Versus Placebo in Scleroderma Lung Study

TypeinterventionalSponsorThe University of Texas Health Science Center, HoustonRan1999 to 2013Enrolled158ConditionsLung Diseases, Pulmonary Fibrosis, Systemic Scleroderma, Scleroderma, SystemicArmsCyclophosphamide, Placebo
NCT00883129 phase2completednot on this map

Mycophenolate vs. Oral Cyclophosphamide in Scleroderma Interstitial Lung Disease (Scleroderma Lung Study II)

TypeinterventionalSponsorMichael RothRan2009 to 2015Enrolled142ConditionsScleroderma, Interstitial Lung DiseaseArmsMycophenolate mofetil, Cyclophosphamide, Placebo
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

7 authors.

Elizabeth R VolkmannDavid Geffen School of Medicine, University of California, Los Angeles, 1000 Veteran Ave. Ste 32-59, Los Angeles, CA, 90095, USA. elizabethv@elizabethvolkmann.com.
Holly WilhalmeDavid Geffen School of Medicine, University of California, Los Angeles, 1000 Veteran Ave. Ste 32-59, Los Angeles, CA, 90095, USA.
Sam GoodDavid Geffen School of Medicine, University of California, Los Angeles, 1000 Veteran Ave. Ste 32-59, Los Angeles, CA, 90095, USA.
Grace Hyun J KimDavid Geffen School of Medicine, University of California, Los Angeles, 1000 Veteran Ave. Ste 32-59, Los Angeles, CA, 90095, USA.
Jonathan GoldinDavid Geffen School of Medicine, University of California, Los Angeles, 1000 Veteran Ave. Ste 32-59, Los Angeles, CA, 90095, USA.
Michael D RothDavid Geffen School of Medicine, University of California, Los Angeles, 1000 Veteran Ave. Ste 32-59, Los Angeles, CA, 90095, USA.
Donald P TashkinDavid Geffen School of Medicine, University of California, Los Angeles, 1000 Veteran Ave. Ste 32-59, Los Angeles, CA, 90095, USA.

Funding

Identifying predictors of treatment response in systemic sclerosis-related interstitial lung diseaseK23HL150237 · NHLBI · UNIVERSITY OF CALIFORNIA LOS ANGELES · PI VOLKMANN, ELIZABETH R · 2020 to 2024
$910k
NHLBI NIH HHS K23 HL150237
6 · The paper itself

Abstract

backgroundThe forced vital capacity (FVC) is the most commonly used endpoint in registrational trials for systemic sclerosis-associated interstitial lung disease (SSc-ILD). However, the FVC has known methodological pitfalls, is affected by extra-pulmonary SSc manifestations and may not be clinically meaningful to patients. Combining individual outcomes into a composite endpoint is an attractive alternative for measuring treatment response and augmenting statistical efficiency in SSc-ILD trials.

methodsWe previously developed a composite endpoint for SSc-ILD using data from the Scleroderma Lung Study (SLS) I (comparing cyclophosphamide versus placebo for SSc-ILD), which included physiological (FVC), radiological (quantitative extent of fibrosis in the zone of maximum involvement) and patient-reported outcomes (transitional dyspnea index and health assessment disability questionnaire), which demonstrated a more robust treatment effect of cyclophosphamide than the FVC alone. The purpose of this post-hoc analysis was to validate this composite endpoint in an external clinical trial cohort (SLS II [cyclophosphamide versus mycophenolate for SSc-ILD). A secondary goal was to determine whether the composite endpoint predicted long-term mortality in SLS I and II.

resultsSeventy-two of the 142 randomized participants in SLS II had all composite endpoint components at 24 months and were included in this analysis. In both SLS I and II, the standardized effect size (Cohen's d) was greater when the composite endpoint model was applied than when the FVC alone model was applied. In SLS I and II, the composite endpoint was a better predictor of long-term survival (HR 0.76 vs. 0.98 and 0.59 vs. 0.98, for the composite index vs. FVC Cox proportional hazards models in SLS I and II, respectively). Patients with high composite outcomes scores in both SLS I and II had significantly worse long-term survival than patients with low scores (p = 0.039 for log-rank test).

conclusionThe results of this post-hoc analysis provide further evidence that a composite endpoint comprised of physiological, radiological and patient-reported outcomes is a promising endpoint for SSc-ILD trials. Future validation studies are needed.

trial registrationSLS II: NCT00883129 (Date of registration April 17, 2009); SLS I: NCT00004563 (Date of registration: February 10, 2000).

Indexed as

Endpoint DeterminationLung Diseases, InterstitialScleroderma, SystemicAdultAgedCohort StudiesCyclophosphamideFemaleHumansImmunosuppressive AgentsMaleMiddle AgedMycophenolic AcidTreatment OutcomeVital CapacityCyclophosphamideImmunosuppressive AgentsMycophenolic AcidInterstitial lung diseasePatient outcome assessmentRandomized controlled trialSystemic sclerosis

Identifiers

PMID41316297
PMCPMC12661867

What OpenQuestion holds

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LicenceCC BY
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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.