Evidence map›Paper›PMID 29688579›Full record

Trial reportAllergy2018

Evaluation of avoralstat, an oral kallikrein inhibitor, in a Phase 3 hereditary angioedema prophylaxis trial: The OPuS-2 study.

M A Riedl, E Aygören-Pürsün, J Baker, H Farkas, J Anderson, J A Bernstein, L Bouillet, P Busse, M Manning, M Magerl and 27 more

Open access · hybridAbstract readClinical Trial, Phase IIIMulticenter StudyRandomized Controlled Trial
PubMed Full text at PMC Publisher
In one paragraph

Trial report in Allergy, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
19citing papers in PubMed, 1 pooled it
3.3field-weighted citation impact, top 7% 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.

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

19 citing papers in PubMed, 1 synthesis or guideline pooled it, 40 citations in OpenAlex.

  1. Interventions for the long-term prevention of hereditary angioedema attacks.The Cochrane database of systematic reviews · 2022
    Pooled it
  2. Trial
  3. Trial
  4. Review
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  6. Review
  7. Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. [Hereditary angioedema].Der Internist · 2019
    Review
  14. Advances in drug allergy, urticaria, angioedema, and anaphylaxis in 2018.The Journal of allergy and clinical immunology · 2019
    Review
  15. Article
  16. Review
  17. Review
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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

37 authors at 20 institutions in 8 countries.

M A RiedlDivision of Rheumatology, Allergy & Immunology, University of California San Diego, San Diego, CA, USA.ORCID 0000-0003-3460-1544
E Aygören-PürsünDepartment for Children and Adolescents, University Hospital Frankfurt, Frankfurt, Germany.
J BakerBaker Allergy Asthma Dermatology Research Center, Portland, OR, USA.
H Farkas3rd Department of Internal Medicine, Semmelweis University, Budapest, Hungary.ORCID 0000-0003-2929-1721
J AndersonClinical Research Center of Alabama, Birmingham, AL, USA.
J A BernsteinDepartment of Internal Medicine, University of Cincinnati, Cincinnati, OH, USA.ORCID 0000-0002-3476-1196
L BouilletInternal Medicine, National Reference Centre of Angioedema, Grenoble University Hospital, Grenoble, France.ORCID 0000-0001-8245-4767
P BusseDivision of Clinical Immunology and Allergy, Department of Medicine, Icahn School of Medicine at Mount Sinai, New York, NY, USA.
M ManningMedical Research of Arizona, Allergy, Asthma & Immunology Associates, Scottsdale, AZ, USA.
M MagerlDermatology, Venerology and Allergology, Charite - Universitätsmedizin Berlin, Berlin, Germany.
M GompelsImmunology, North Bristol NHS Trust, Bristol, UK.
A P HuissoonDepartment of Allergy and Immunology, Heartlands Hospital, Birmingham, UK.
H LonghurstImmunology, Addenbrookes Hospital, Cambridge University Hospitals, Cambridge, UK.
W LumryAllergy and Asthma Research Associates Research Center, Dallas, TX, USA.
B RitchieDivision of Hematology, Department of Medicine, University of Alberta, Edmonton, AB, Canada.
R ShapiroImmunology, Midwest Immunology Clinic, Plymouth, MN, USA.
D SoteresAsthma and Allergy Associates PC, Colorado Springs, CO, USA.
A BanerjiDivision of Rheumatology, Allergy& Immunology, Department of Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA, USA.
M CancianDepartment of Medicine, University of Padova, Padova, Italy.
D T JohnstonAsthma & Allergy Specialists, P.A., Charlotte, NC, USA.
T J CraigDepartment of Medicine and Pediatrics, Penn State Hershey Allergy Asthma, and Immunology, Hershey, PA, USA.
D LaunayInternal Medicine, CHRU Lille, France, France.
H H LiInstitute for Asthma and Allergy, Chevy Chase, MD, USA.
M LiebhaberAllergy and Immunology, Sansum Clinic, Santa Barbara, CA, USA.
T NickelAllergy & Immunology, Allergy Clinic of Tulsa, Tulsa, OK, USA.
J OffenbergerAllergy and Asthma Relief Experts, Grenada Hills, CA, USA.
W RaeAllergy & Clinical Immunology, University Hospital Southampton NHS Foundation Trust, Southampton, UK.
R SchrijversLaboratory of Clinical Immunology, KU Leuven, Leuven, Belgium.
M TriggianiDivision of Allergy and Clinical Immunology, University of Salerno, Salerno, Italy.
H J WednerDivision of Allergy and Immunology, Washington University School of Medicine, St. Louis, MO, USA.
S DoboBiocryst Pharmaceuticals, Durham, NC, USA.
M CornpropstBiocryst Pharmaceuticals, Durham, NC, USA.
D ClemonsBiocryst Pharmaceuticals, Durham, NC, USA.
L FangStatistics, PharStat, Inc., Raleigh, NC, USA.
P CollisBiocryst Pharmaceuticals, Durham, NC, USA.
W P SheridanBiocryst Pharmaceuticals, Durham, NC, USA.ORCID 0000-0001-8320-1323
M MaurerDepartment of Dermatology and Allergy, Charité - Universitätsmedizin Berlin, Berlin, Germany.ORCID 0000-0002-4121-481X
BioCryst Pharmaceuticals (United States) · USCharité - Universitätsmedizin Berlin · DEAllergy Associates Research Center · USAllergy Clinic of Tulsa · USAsthma and Allergy Specialists · USCentre Hospitalier Universitaire de Grenoble · FRCentre Hospitalier Universitaire de Lille · FRClinical Research Management · USDermatology Research Center · USGoethe University Frankfurt · DEHarvard University · USHeartlands Hospital · GBIcahn School of Medicine at Mount Sinai · USInstitute for Asthma and Allergy · USKU Leuven · BEMidwest Therapeutic Endoscopy · USNorth Bristol NHS Trust · GBPenn State Milton S. Hershey Medical Center · USSansum Medical Clinic · USSemmelweis University · HU

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundEffective inhibition of plasma kallikrein may have significant benefits for patients with hereditary angioedema due to deficiency of C1 inhibitor (C1-INH-HAE) by reducing the frequency of angioedema attacks. Avoralstat is a small molecule inhibitor of plasma kallikrein. This study (OPuS-2) evaluated the efficacy and safety of prophylactic avoralstat 300 or 500 mg compared with placebo.

methodsOPuS-2 was a Phase 3, multicenter, randomized, double-blind, placebo-controlled, parallel-group study. Subjects were administered avoralstat 300 mg, avoralstat 500 mg, or placebo orally 3 times per day for 12 weeks. The primary efficacy endpoint was the angioedema attack rate based on adjudicator-confirmed attacks.

resultsA total of 110 subjects were randomized and dosed. The least squares (LS) mean attack rates per week were 0.589, 0.675, and 0.593 for subjects receiving avoralstat 500 mg, avoralstat 300 mg, and placebo, respectively. Overall, 1 subject in each of the avoralstat groups and no subjects in the placebo group were attack-free during the 84-day treatment period. The LS mean duration of all confirmed attacks was 25.4, 29.4, and 31.4 hours for the avoralstat 500 mg, avoralstat 300 mg, and placebo groups, respectively. Using the Angioedema Quality of Life Questionnaire (AE-QoL), improved QoL was observed for the avoralstat 500 mg group compared with placebo. Avoralstat was generally safe and well tolerated.

conclusionsAlthough this study did not demonstrate efficacy of avoralstat in preventing angioedema attacks in C1-INH-HAE, it provided evidence of shortened angioedema episodes and improved QoL in the avoralstat 500 mg treatment group compared with placebo.

Indexed as

Administration, OralAdultAngioedemas, HereditaryDisease ProgressionEnzyme InhibitorsFemaleHumansMaleMiddle AgedPlasma KallikreinQuality of LifeRecurrenceTreatment OutcomeEnzyme InhibitorsPlasma KallikreinC1 inhibitorhereditary angioedemaoral kallikrein inhibitorprophylaxis

Identifiers

PMID29688579
PMCPMC6175137
OpenAlexW2802058432

What OpenQuestion holds

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LicenceCC BY-NC-ND
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Registered trials

None linked

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.