Evidence map›Paper›PMID 25482425›Full record

Trial reportThe New England journal of medicine2015

Factor XI antisense oligonucleotide for prevention of venous thrombosis.

Harry R Büller, Claudette Bethune, Sanjay Bhanot, David Gailani, Brett P Monia, Gary E Raskob, Annelise Segers, Peter Verhamme, Jeffrey I Weitz, FXI-ASO TKA Investigators

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

Trial report in The New England journal of medicine, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT01713361 (An Open-label, Randomized, Active Comparator-Controlled, Adaptive Parallel-group Phase 2 Study to Assess the Safety and Efficacy of Multiple Doses of ISIS 416858 Administered Subcutaneously to Patients Undergoing Total Knee Arthroplasty), which is not on this map. Cited by 278 papers, 9 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
278citing papers in PubMed, 9 pooled it
27.8field-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.

NCT01713361 phase2completednot on this map

An Open-label, Randomized, Active Comparator-Controlled, Adaptive Parallel-group Phase 2 Study to Assess the Safety and Efficacy of Multiple Doses of ISIS 416858 Administered Subcutaneously to Patients Undergoing Total Knee Arthroplasty

TypeinterventionalSponsorIonis Pharmaceuticals, Inc.Ran2012 to 2014Enrolled315ConditionsVenous ThromboembolismArmsISIS-FXIRx Dose #2, ISIS-FXIRx Dose #3, Enoxaparin
3 · Its place in the literature

Who cites it

278 citing papers in PubMed, 9 syntheses or guidelines pooled it, 612 citations in OpenAlex.

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  5. Déjà vu all over again: a recurrent flaw in anticoagulant study design.Journal of thrombosis and haemostasis : JTH · 2025
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  6. Anticoagulation for people receiving long-term haemodialysis.The Cochrane database of systematic reviews · 2024
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  18. Milvexian for the Prevention of Venous Thromboembolism.The New England journal of medicine · 2021
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218 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

10 authors at 7 institutions in 4 countries.

Harry R BüllerFrom the Department of Vascular Medicine, Academic Medical Center, University of Amsterdam (H.R.B.), and International Trial Expertise Advisory and Services (ITREAS) (A.S.) - both in Amsterdam; Isis Pharmaceuticals, Carlsbad, CA (C.B., S.B., B.P.M.); Department of Pathology, Microbiology and Immunology, Vanderbilt University, Nashville (D.G.); University of Oklahoma Health Sciences Center, College of Public Health, Oklahoma City (G.E.R.); KU Leuven Department of Cardiovascular Sciences, Vascular Medicine and Hemostasis, Leuven, Belgium (P.V.); and the Thrombosis and Atherosclerosis Research Institute and McMaster University, Hamilton, ON, Canada (J.I.W.).
Claudette Bethune
Sanjay Bhanot
David Gailani
Brett P Monia
Gary E Raskob
Annelise Segers
Peter Verhamme
Jeffrey I Weitz
FXI-ASO TKA Investigators
Ionis Pharmaceuticals (United States) · USAcademic Medical Center · NLAtria · NLKU Leuven · BEThrombosis and Atherosclerosis Research Institute · CAUniversity of Oklahoma Health Sciences Center · USVanderbilt University · US

Funding

Physiology and Molecular Biology of Factor XIR01HL058837 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI GAILANI, DAVID · 1997 to 2017
$6.4M
Factor Xl in Vascular ThrombosisR01HL081326 · NHLBI · VANDERBILT UNIVERSITY MEDICAL CENTER · PI GAILANI, DAVID · 2007 to 2017
$3.5M
NHLBI NIH HHS R01 HL058837NHLBI NIH HHS R01 HL081326
6 · The paper itself

Abstract

backgroundExperimental data indicate that reducing factor XI levels attenuates thrombosis without causing bleeding, but the role of factor XI in the prevention of postoperative venous thrombosis in humans is unknown. FXI-ASO (ISIS 416858) is a second-generation antisense oligonucleotide that specifically reduces factor XI levels. We compared the efficacy and safety of FXI-ASO with those of enoxaparin in patients undergoing total knee arthroplasty.

methodsIn this open-label, parallel-group study, we randomly assigned 300 patients who were undergoing elective primary unilateral total knee arthroplasty to receive one of two doses of FXI-ASO (200 mg or 300 mg) or 40 mg of enoxaparin once daily. The primary efficacy outcome was the incidence of venous thromboembolism (assessed by mandatory bilateral venography or report of symptomatic events). The principal safety outcome was major or clinically relevant nonmajor bleeding.

resultsAround the time of surgery, the mean (±SE) factor XI levels were 0.38±0.01 units per milliliter in the 200-mg FXI-ASO group, 0.20±0.01 units per milliliter in the 300-mg FXI-ASO group, and 0.93±0.02 units per milliliter in the enoxaparin group. The primary efficacy outcome occurred in 36 of 134 patients (27%) who received the 200-mg dose of FXI-ASO and in 3 of 71 patients (4%) who received the 300-mg dose of FXI-ASO, as compared with 21 of 69 patients (30%) who received enoxaparin. The 200-mg regimen was noninferior, and the 300-mg regimen was superior, to enoxaparin (P<0.001). Bleeding occurred in 3%, 3%, and 8% of the patients in the three study groups, respectively.

conclusionsThis study showed that factor XI contributes to postoperative venous thromboembolism; reducing factor XI levels in patients undergoing elective primary unilateral total knee arthroplasty was an effective method for its prevention and appeared to be safe with respect to the risk of bleeding. (Funded by Isis Pharmaceuticals; FXI-ASO TKA ClinicalTrials.gov number, NCT01713361.).

Indexed as

Arthroplasty, Replacement, KneeAdultAgedAnticoagulantsBlood CoagulationClinical ProtocolsEnoxaparinFactor XIFemaleHemorrhageHumansLength of StayMaleMiddle AgedOligonucleotidesOligonucleotides, AntisenseAnticoagulantsEnoxaparinFactor XIISIS 416858OligonucleotidesOligonucleotides, Antisense

Identifiers

PMID25482425
PMCPMC4367537
OpenAlexW2102719739

What OpenQuestion holds

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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.