Evidence map›Paper›PMID 34780683›Full record

Trial reportThe New England journal of medicine2021

Milvexian for the Prevention of Venous Thromboembolism.

Jeffrey I Weitz, John Strony, Walter Ageno, David Gailani, Elaine M Hylek, Michael R Lassen, Kenneth W Mahaffey, Ravi S Notani, Robin Roberts, Annelise Segers and 2 more

Registry-linked trialOpen access · bronzeAbstract readClinical Trial, Phase IIComparative Study
PubMed Full text at PMC Publisher
In one paragraph

Trial report in The New England journal of medicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03891524 (A Randomized, Open-Label, Study Drug-Dose Blind, Multicenter Study to Evaluate the Efficacy and Safety of JNJ-70033093), which is not on this map. Cited by 131 papers, 8 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
131citing papers in PubMed, 8 pooled it
23.9field-weighted citation impact, top 1% 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.

NCT03891524 phase2completednot on this map

A Randomized, Open-Label, Study Drug-Dose Blind, Multicenter Study to Evaluate the Efficacy and Safety of JNJ-70033093 (BMS-986177), an Oral Factor XIa Inhibitor, Versus Subcutaneous Enoxaparin in Subjects Undergoing Elective Total Knee Replacement Surgery

TypeinterventionalSponsorJanssen Research & Development, LLCRan2019 to 2021Enrolled1,242ConditionsArthroplasty, Replacement, KneeArmsJNJ-70033093 25 mg, JNJ-70033093 50 mg, JNJ-70033093 100 mg, JNJ-70033093 200 mg, Placebo
3 · Its place in the literature

Who cites it

131 citing papers in PubMed, 8 syntheses or guidelines pooled it, 240 citations in OpenAlex.

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  4. Déjà vu all over again: a recurrent flaw in anticoagulant study design.Journal of thrombosis and haemostasis : JTH · 2025
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71 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

12 authors at 8 institutions in 3 countries.

Jeffrey I WeitzFrom the Thrombosis and Atherosclerosis Research Institute and McMaster University (J.I.W., R.R.) - both in Hamilton, ON, Canada; Janssen Research and Development, Raritan, NJ (J.S., R.S.N.); the University of Insubria, Varese, Italy (W.A.); Vanderbilt University Medical Center, Nashville (D.G.); Boston University School of Medicine, Boston (E.M.H.); Gildhøj Private Hospital, Copenhagen (M.R.L.); Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA (K.W.M.); International Trial Expertise Advisory and Services, Amsterdam (A.S.); and Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.).
John StronyFrom the Thrombosis and Atherosclerosis Research Institute and McMaster University (J.I.W., R.R.) - both in Hamilton, ON, Canada; Janssen Research and Development, Raritan, NJ (J.S., R.S.N.); the University of Insubria, Varese, Italy (W.A.); Vanderbilt University Medical Center, Nashville (D.G.); Boston University School of Medicine, Boston (E.M.H.); Gildhøj Private Hospital, Copenhagen (M.R.L.); Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA (K.W.M.); International Trial Expertise Advisory and Services, Amsterdam (A.S.); and Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.).
Walter AgenoFrom the Thrombosis and Atherosclerosis Research Institute and McMaster University (J.I.W., R.R.) - both in Hamilton, ON, Canada; Janssen Research and Development, Raritan, NJ (J.S., R.S.N.); the University of Insubria, Varese, Italy (W.A.); Vanderbilt University Medical Center, Nashville (D.G.); Boston University School of Medicine, Boston (E.M.H.); Gildhøj Private Hospital, Copenhagen (M.R.L.); Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA (K.W.M.); International Trial Expertise Advisory and Services, Amsterdam (A.S.); and Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.).
David GailaniFrom the Thrombosis and Atherosclerosis Research Institute and McMaster University (J.I.W., R.R.) - both in Hamilton, ON, Canada; Janssen Research and Development, Raritan, NJ (J.S., R.S.N.); the University of Insubria, Varese, Italy (W.A.); Vanderbilt University Medical Center, Nashville (D.G.); Boston University School of Medicine, Boston (E.M.H.); Gildhøj Private Hospital, Copenhagen (M.R.L.); Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA (K.W.M.); International Trial Expertise Advisory and Services, Amsterdam (A.S.); and Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.).
Elaine M HylekFrom the Thrombosis and Atherosclerosis Research Institute and McMaster University (J.I.W., R.R.) - both in Hamilton, ON, Canada; Janssen Research and Development, Raritan, NJ (J.S., R.S.N.); the University of Insubria, Varese, Italy (W.A.); Vanderbilt University Medical Center, Nashville (D.G.); Boston University School of Medicine, Boston (E.M.H.); Gildhøj Private Hospital, Copenhagen (M.R.L.); Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA (K.W.M.); International Trial Expertise Advisory and Services, Amsterdam (A.S.); and Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.).
Michael R LassenFrom the Thrombosis and Atherosclerosis Research Institute and McMaster University (J.I.W., R.R.) - both in Hamilton, ON, Canada; Janssen Research and Development, Raritan, NJ (J.S., R.S.N.); the University of Insubria, Varese, Italy (W.A.); Vanderbilt University Medical Center, Nashville (D.G.); Boston University School of Medicine, Boston (E.M.H.); Gildhøj Private Hospital, Copenhagen (M.R.L.); Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA (K.W.M.); International Trial Expertise Advisory and Services, Amsterdam (A.S.); and Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.).
Kenneth W MahaffeyFrom the Thrombosis and Atherosclerosis Research Institute and McMaster University (J.I.W., R.R.) - both in Hamilton, ON, Canada; Janssen Research and Development, Raritan, NJ (J.S., R.S.N.); the University of Insubria, Varese, Italy (W.A.); Vanderbilt University Medical Center, Nashville (D.G.); Boston University School of Medicine, Boston (E.M.H.); Gildhøj Private Hospital, Copenhagen (M.R.L.); Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA (K.W.M.); International Trial Expertise Advisory and Services, Amsterdam (A.S.); and Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.).
Ravi S NotaniFrom the Thrombosis and Atherosclerosis Research Institute and McMaster University (J.I.W., R.R.) - both in Hamilton, ON, Canada; Janssen Research and Development, Raritan, NJ (J.S., R.S.N.); the University of Insubria, Varese, Italy (W.A.); Vanderbilt University Medical Center, Nashville (D.G.); Boston University School of Medicine, Boston (E.M.H.); Gildhøj Private Hospital, Copenhagen (M.R.L.); Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA (K.W.M.); International Trial Expertise Advisory and Services, Amsterdam (A.S.); and Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.).
Robin RobertsFrom the Thrombosis and Atherosclerosis Research Institute and McMaster University (J.I.W., R.R.) - both in Hamilton, ON, Canada; Janssen Research and Development, Raritan, NJ (J.S., R.S.N.); the University of Insubria, Varese, Italy (W.A.); Vanderbilt University Medical Center, Nashville (D.G.); Boston University School of Medicine, Boston (E.M.H.); Gildhøj Private Hospital, Copenhagen (M.R.L.); Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA (K.W.M.); International Trial Expertise Advisory and Services, Amsterdam (A.S.); and Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.).
Annelise SegersFrom the Thrombosis and Atherosclerosis Research Institute and McMaster University (J.I.W., R.R.) - both in Hamilton, ON, Canada; Janssen Research and Development, Raritan, NJ (J.S., R.S.N.); the University of Insubria, Varese, Italy (W.A.); Vanderbilt University Medical Center, Nashville (D.G.); Boston University School of Medicine, Boston (E.M.H.); Gildhøj Private Hospital, Copenhagen (M.R.L.); Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA (K.W.M.); International Trial Expertise Advisory and Services, Amsterdam (A.S.); and Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.).
Gary E RaskobFrom the Thrombosis and Atherosclerosis Research Institute and McMaster University (J.I.W., R.R.) - both in Hamilton, ON, Canada; Janssen Research and Development, Raritan, NJ (J.S., R.S.N.); the University of Insubria, Varese, Italy (W.A.); Vanderbilt University Medical Center, Nashville (D.G.); Boston University School of Medicine, Boston (E.M.H.); Gildhøj Private Hospital, Copenhagen (M.R.L.); Stanford Center for Clinical Research, Department of Medicine, Stanford University School of Medicine, Stanford, CA (K.W.M.); International Trial Expertise Advisory and Services, Amsterdam (A.S.); and Hudson College of Public Health, University of Oklahoma Health Sciences Center, Oklahoma City (G.E.R.).
AXIOMATIC-TKR Investigators
Janssen (United States) · USBoston University · USCenter for Clinical Research (United States) · USMcMaster University · CAThrombosis and Atherosclerosis Research Institute · CAUniversity of Insubria · ITUniversity of Oklahoma Health Sciences Center · USVanderbilt University Medical Center · US

Funding

Biochemistry and Pathophysiology of Factor XI and Contact ActivationR35HL140025 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI GAILANI, DAVID · 2018 to 2024
$5.5M
NHLBI NIH HHS R35 HL140025
6 · The paper itself

Abstract

backgroundFactor XIa inhibitors for the prevention and treatment of venous and arterial thromboembolism may be more effective and result in less bleeding than conventional anticoagulants. Additional data are needed regarding the efficacy and safety of milvexian, an oral factor XIa inhibitor.

methodsIn this parallel-group, phase 2 trial, we randomly assigned 1242 patients undergoing knee arthroplasty to receive one of seven postoperative regimens of milvexian (25 mg, 50 mg, 100 mg, or 200 mg twice daily or 25 mg, 50 mg, or 200 mg once daily) or enoxaparin (40 mg once daily). The primary efficacy outcome was venous thromboembolism (which was a composite of asymptomatic deep-vein thrombosis, confirmed symptomatic venous thromboembolism, or death from any cause). The principal safety outcome was bleeding.

resultsAmong the patients receiving milvexian twice daily, venous thromboembolism developed in 27 of 129 (21%) taking 25 mg, in 14 of 124 (11%) taking 50 mg, in 12 of 134 (9%) taking 100 mg, and in 10 of 131 (8%) taking 200 mg. Among those receiving milvexian once daily, venous thromboembolism developed in 7 of 28 (25%) taking 25 mg, in 30 of 127 (24%) taking 50 mg, and in 8 of 123 (7%) taking 200 mg, as compared with 54 of 252 patients (21%) taking enoxaparin. The dose-response relationship with twice-daily milvexian was significant (one-sided P<0.001), and the 12% incidence of venous thromboembolism with twice-daily milvexian was significantly lower than the prespecified benchmark of 30% (one-sided P<0.001). Bleeding of any severity occurred in 38 of 923 patients (4%) taking milvexian and in 12 of 296 patients (4%) taking enoxaparin; major or clinically relevant nonmajor bleeding occurred in 1% and 2%, respectively; and serious adverse events were reported in 2% and 4%, respectively.

conclusionsPostoperative factor XIa inhibition with oral milvexian in patients undergoing knee arthroplasty was effective for the prevention of venous thromboembolism and was associated with a low risk of bleeding. (Funded by Bristol Myers Squibb and Janssen Research and Development; AXIOMATIC-TKR ClinicalTrials.gov number, NCT03891524.).

Indexed as

Arthroplasty, Replacement, KneeAdministration, OralAgedAged, 80 and overAnticoagulantsDose-Response Relationship, DrugEnoxaparinFactor XIaFemaleHumansMaleMiddle AgedPostoperative ComplicationsPyrimidinesTriazolesVenous ThromboembolismAnticoagulantsEnoxaparinFactor XIamilvexianPyrimidinesTriazoles

Identifiers

PMID34780683
PMCPMC9540352
OpenAlexW3212517452

What OpenQuestion holds

Textmetadata
LicenceTDM
Read underepoch 390

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.