Evidence map›Paper›PMID 27570089›Full record

Trial reportThe Lancet. Haematology2016

Rivaroxaban versus warfarin to treat patients with thrombotic antiphospholipid syndrome, with or without systemic lupus erythematosus (RAPS): a randomised, controlled, open-label, phase 2/3, non-inferiority trial.

Hannah Cohen, Beverley J Hunt, Maria Efthymiou, Deepa R J Arachchillage, Ian J Mackie, Simon Clawson, Yvonne Sylvestre, Samuel J Machin, Maria L Bertolaccini, Maria Ruiz-Castellano and 5 more

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

Trial report in The Lancet. Haematology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06929182 (OBServaToIre National Des Patients AnTiphospholipidEs traités Par Anticoagulants Oraux Directs), which is not on this map. Cited by 145 papers, 11 of them syntheses that pooled it.

0numbers the graph read from it
0cells of the map it votes in
145citing papers in PubMed, 11 pooled it
47.9field-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.

NCT06929182 not yet recruitingnot on this mapstarted 2025, after this paper: background citation

OBServaToIre National Des Patients AnTiphospholipidEs traités Par Anticoagulants Oraux Directs

Typeobservational_patient_registrySponsorCentral Hospital, Nancy, FranceRan2025 to 2035Enrolled500ConditionsAntiphospholipid Syndrome (APS), Direct Oral Anticoagulants (DOACs), Thrombotic and Bleeding Events, SafetyArms"non-high risk" thrombotic APS patients treated with DOAC
3 · Its place in the literature

Who cites it

145 citing papers in PubMed, 11 syntheses or guidelines pooled it, 394 citations in OpenAlex.

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  11. Evaluating the Efficacy and Safety of Direct Oral Anticoagulants Compared to Vitamin K Antagonists in Patients with Antiphospholipid Syndrome: Updated Systematic Review and Meta-Analysis.Clinical and applied thrombosis/hemostasis : official journal of the International Academy of Clinical and Applied Thrombosis/Hemostasis
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85 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

15 authors at 4 institutions in 1 country.

Hannah CohenDepartment of Haematology, University College London Hospitals NHS Foundation Trust, London, UK; Haemostasis Research Unit, Department of Haematology, University College London, London, UK. Electronic address: hannah.cohen@ucl.ac.uk.
Beverley J HuntDepartment of Thrombosis and Haemophilia, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, UK; Department of Haematology, King's College London, London, UK.
Maria EfthymiouHaemostasis Research Unit, Department of Haematology, University College London, London, UK.
Deepa R J ArachchillageHaemostasis Research Unit, Department of Haematology, University College London, London, UK.
Ian J MackieHaemostasis Research Unit, Department of Haematology, University College London, London, UK.
Simon ClawsonComprehensive Clinical Trials Unit, University College London, London, UK.
Yvonne SylvestreComprehensive Clinical Trials Unit, University College London, London, UK.
Samuel J MachinHaemostasis Research Unit, Department of Haematology, University College London, London, UK.
Maria L BertolacciniAcademic Department of Vascular Surgery, Cardiovascular Division, Faculty of Life Sciences and Medicine, King's College London, London, UK.
Maria Ruiz-CastellanoLupus Research Unit, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, UK.
Nicola MuirheadComprehensive Clinical Trials Unit, University College London, London, UK.
Caroline J DoréComprehensive Clinical Trials Unit, University College London, London, UK.
Munther KhamashtaLupus Research Unit, Guy's and St Thomas' Hospitals NHS Foundation Trust, London, UK; Lupus Research Unit, Division of Women's Health, King's College London, London, UK.
David A IsenbergDepartment of Rheumatology, University College London Hospitals NHS Foundation Trust, London, UK; Centre for Rheumatology, Division of Medicine, University College London, London, UK.
RAPS trial investigators
University College London · GBSt Thomas' Hospital · GBKing's College London · GBUniversity College London Hospitals NHS Foundation Trust · GB

Funding

Medical Research Council MC_U122886349Medical Research Council MC_UU_12023/14Versus Arthritis 19708
6 · The paper itself

Abstract

backgroundRivaroxaban is established for the treatment and secondary prevention of venous thromboembolism, but whether it is useful in patients with antiphospholipid syndrome is uncertain.

methodsThis randomised, controlled, open-label, phase 2/3, non-inferiority trial, done in two UK hospitals, included patients with antiphospholipid syndrome who were taking warfarin for previous venous thromboembolism, with a target international normalised ratio of 2·5. Patients were randomly assigned 1:1 to continue with warfarin or receive 20 mg oral rivaroxaban daily. Randomisation was done centrally, stratified by centre and patient type (with vs without systemic lupus erythematosus). The primary outcome was percentage change in endogenous thrombin potential (ETP) from randomisation to day 42, with non-inferiority set at less than 20% difference from warfarin in mean percentage change. Analysis was by modified intention to treat. Other thrombin generation parameters, thrombosis, and bleeding were also assessed. Treatment effect was measured as the ratio of rivaroxaban to warfarin for thrombin generation. This trial is registered with the ISRCTN registry, number ISRCTN68222801.

findingsOf 116 patients randomised between June 5, 2013, and Nov 11, 2014, 54 who received rivaroxaban and 56 who received warfarin were assessed. At day 42, ETP was higher in the rivaroxaban than in the warfarin group (geometric mean 1086 nmol/L per min, 95% CI 957-1233 vs 548, 484-621, treatment effect 2·0, 95% CI 1·7-2·4, p<0·0001). Peak thrombin generation was lower in the rivaroxaban group (56 nmol/L, 95% CI 47-66 vs 86 nmol/L, 72-102, treatment effect 0·6, 95% CI 0·5-0·8, p=0·0006). No thrombosis or major bleeding were seen. Serious adverse events occurred in four patients in each group.

interpretationETP for rivaroxaban did not reach the non-inferiority threshold, but as there was no increase in thrombotic risk compared with standard-intensity warfarin, this drug could be an effective and safe alternative in patients with antiphospholipid syndrome and previous venous thromboembolism.

fundingArthritis Research UK, Comprehensive Clinical Trials Unit at UCL, LUPUS UK, Bayer, National Institute for Health Research Biomedical Research Centre.

Indexed as

AnticoagulantsAntiphospholipid SyndromeEquivalence Trials as TopicFactor Xa InhibitorsFemaleFollow-Up StudiesHumansLupus Erythematosus, SystemicMaleMiddle AgedPrevalenceRivaroxabanSurvival RateThrombosisTreatment OutcomeUnited KingdomAnticoagulantsFactor Xa InhibitorsRivaroxabanWarfarin

Identifiers

PMID27570089
PMCPMC5010562
OpenAlexW2514539105

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.