Evidence map›Paper›PMID 31481106›Full record

Trial reportArthritis research & therapy2019

A multicenter randomized, double-blind, placebo-controlled pilot study to assess the efficacy and safety of riociguat in systemic sclerosis-associated digital ulcers.

Vivek Nagaraja, Cathie Spino, Erica Bush, Pei-Suen Tsou, Robyn T Domsic, Robert Lafyatis, Tracy Frech, Jessica K Gordon, Virginia D Steen, Dinesh Khanna

Registry-linked trialOpen access · goldAbstract readMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Arthritis research & therapy, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT02915835 (A Multi-center Randomized, Double Blind, Placebo-controlled, Pilot Study to Assess the Efficacy and Safety of Riociguat in Scleroderma - Associated Digital Ulcers), which is not on this map. Cited by 8 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed, 1 pooled it
2.3field-weighted citation impact, top 12% of its field
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.

NCT02915835 phase2completednot on this map

A Multi-center Randomized, Double Blind, Placebo-controlled, Pilot Study to Assess the Efficacy and Safety of Riociguat in Scleroderma - Associated Digital Ulcers

TypeinterventionalSponsorDinesh Khanna, MD, MSRan2016 to 2018Enrolled17ConditionsScleroderma, Digital UlcersArmsRiociguat, Placebo
3 · Its place in the literature

Who cites it

8 citing papers in PubMed, 1 synthesis or guideline pooled it, 29 citations in OpenAlex.

  1. Pooled it
  2. Article
  3. Review
  4. Review
  5. Review
  6. Article
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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 at 6 institutions in 1 country.

Vivek NagarajaDivision of Rheumatology/Department of Internal Medicine, University of Michigan Scleroderma Program, Suite 7C27, 300 North Ingalls Street, SPC 5422, Ann Arbor, MI, 48109, USA.
Cathie SpinoDepartment of Biostatistics, School of Public Health, University of Michigan, Ann Arbor, MI, USA.
Erica BushDivision of Rheumatology/Department of Internal Medicine, University of Michigan Scleroderma Program, Suite 7C27, 300 North Ingalls Street, SPC 5422, Ann Arbor, MI, 48109, USA.
Pei-Suen TsouDivision of Rheumatology/Department of Internal Medicine, University of Michigan Scleroderma Program, Suite 7C27, 300 North Ingalls Street, SPC 5422, Ann Arbor, MI, 48109, USA.
Robyn T DomsicDivision of Rheumatology and Clinical Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Robert LafyatisDivision of Rheumatology and Clinical Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USA.
Tracy FrechDivision of Rheumatology, University of Utah, Salt Lake City, UT, USA.
Jessica K GordonDivision of Rheumatology, Hospital of Special Surgery, New York, NY, USA.
Virginia D SteenDivision of Rheumatology, Georgetown University Medical Center, Washington, DC, USA.
Dinesh KhannaDivision of Rheumatology/Department of Internal Medicine, University of Michigan Scleroderma Program, Suite 7C27, 300 North Ingalls Street, SPC 5422, Ann Arbor, MI, 48109, USA. khannad@med.umich.edu.
Scleroderma Foundation · USUniversity of Michigan–Ann Arbor · USUniversity of Pittsburgh Medical Center · USGeorgetown University Medical Center · USHospital for Special Surgery · USUniversity of Utah · US

Funding

Outcomes Research in Rheumatic DiseasesK24AR063120 · NIAMS · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI KHANNA, DINESH · 2012 to 2022
$1.6M
Merck Sharp and Dohme noneNIAMS NIH HHS K24 AR063120
6 · The paper itself

Abstract

backgroundTo determine the effect of riociguat, an oral, selective soluble guanylate cyclase stimulator, on the net digital ulcer (DU) burden in systemic sclerosis (SSc).

methodsParticipants with SSc-related active or painful indeterminate DUs were recruited in a multicenter, double-blind, randomized, placebo-controlled, proof-of-concept trial. Eligible participants were required to have at least one visible, active ischemic DU or painful indeterminate DU at screening, located at or distal to the proximal interphalangeal joint and that developed or worsened within 8 weeks prior to screening. Participants were randomized 1:1 to placebo or riociguat in individualized doses (maximum of 2.5 mg three times daily) during an 8-week titration period, followed by an 8-week stable dosing period. This was followed by an optional 16-week open-label extension phase for participants with active DU/reoccurrence of DUs within 1 month of the end of the main treatment phase. The primary endpoint was the change from baseline to week 16 in net ulcer burden (NUB), analyzed using ANCOVA. Other endpoints included plasma biomarkers and proportion of participants with treatment-emergent adverse events (AEs).

resultsSeventeen participants (eight placebo, nine riociguat) were randomized at five centers. Six participants in each group transitioned to the open-label extension. Baseline characteristics were comparable between the treatment groups, except participants randomized to placebo were older and had longer disease duration (p < 0.05). At baseline, the mean (SD) NUB was 2.5 (2.0) in the placebo and 2.4 (1.4) in the riociguat. No significant treatment difference was observed in the change from baseline to 16 weeks in NUB (adjusted mean treatment difference - 0.24, 95% CI (- 1.46, 0.99), p = 0.70). Four participants experienced five serious AE (four in riociguat and one in placebo); none was considered related to study medication. Statistically significant elevation of cGMP was observed at 16 weeks in the riociguat group (p = 0.05); no other biomarkers showed significant changes. In the open-label extension, participants in the riociguat-riociguat arm had complete healing of their DUs.

conclusionIn participants with SSc-DU, treatment with riociguat did not reduce the number of DU net burden compared with placebo at 16 weeks. Open-label extension suggests that longer duration is needed to promote DU healing, which needs to be confirmed in a new trial.

trial registrationClinicalTrials.gov, NCT02915835 . Registered on September 27, 2016.

Indexed as

AdultDose-Response Relationship, DrugDouble-Blind MethodEnzyme ActivatorsFemaleFinger PhalangesFollow-Up StudiesHumansMaleMiddle AgedPilot ProjectsPyrazolesPyrimidinesScleroderma, SystemicSkin UlcerTreatment OutcomeEnzyme ActivatorsPyrazolesPyrimidinesriociguatClinical trialDigital ulcersRiociguatSystemic sclerosis

Identifiers

PMID31481106
PMCPMC6724329
OpenAlexW2971572185

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.