Rivaroxaban treatment for six weeks versus three months in patients with symptomatic isolated distal deep vein thrombosis: randomised controlled trial

Q: What is the clinical evidence from this study?

Study design: RCT. Population: Symptomatic isolated distal deep vein thrombosis (DVT) (n=402). Intervention: Rivaroxaban (extended 6-week course for a total of 3 months) vs. Placebo once daily for an additional 6 weeks (after initial 6 weeks of standard rivaroxaban). Primary outcome: Recurrent venous thromboembolism (composite of progression of isolated distal DVT, recurrent isolated distal DVT, proximal DVT, symptomatic pulmonary embolism, or fatal pulmonary embolism) during 24-month follow-up (RR 0.59, 95% CI 0.36 to 0.95, p=0.03).

Q: What does this research mean for the field?

Extending rivaroxaban therapy to three months reduces recurrent venous thromboembolism compared with a six-week course in patients with symptomatic isolated distal deep vein thrombosis without increasing major bleeding. Novelty: ClaimNovelty.INCREMENTAL. Consensus alignment: ConsensusAlignment.NEUTRAL.

Walter Ageno; Lorenza Bertù; Eugenio Bucherini; Giuseppe Camporese; Francesco Dentali; M. Iotti; Gianfranco Lessiani; Roberto Parisi; Paolo Prandoni; Michelangelo Sartori; Adriana Visonà; Elisabetta Bigagli; Gualtiero Palareti

doi:10.1136/bmj-2022-072623

November 23, 2022BMJOpen Access

Rivaroxaban treatment for six weeks versus three months in patients with symptomatic isolated distal deep vein thrombosis: randomised controlled trial

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Key result

Extended rivaroxaban cuts recurrent VTE ~41% vs. placebo in isolated distal DVT.

RR 0.59
95% CI 0.36 to 0.95
P=0.03
NNT 13
n=402

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Why the study?

Optimal treatment duration for symptomatic isolated distal deep vein thrombosis was unclear, warranting comparison of two different durations of rivaroxaban.

Does extending rivaroxaban treatment for an additional six weeks (total three months) reduce recurrent venous thromboembolism in adults with symptomatic isolated distal DVT compared to six weeks of treatment?

Key Points

To compare the efficacy and safety of two different treatment durations of rivaroxaban in patients with symptomatic isolated distal deep vein thrombosis.
Randomised, double blind, placebo controlled clinical trial conducted across 28 outpatient clinics specializing in venous thromboembolism in adults (≥18 years) with symptomatic isolated distal deep vein thrombosis (N=402).
Following an initial six-week course of standard-dose rivaroxaban, participants were randomly assigned to receive rivaroxaban 20 mg once daily (n=200) or placebo once daily (n=202) for an additional six weeks, with 24 months of follow-up.
The primary efficacy outcome of recurrent venous thromboembolism occurred in 23 (11%) patients in the rivaroxaban arm versus 39 (19%) in the placebo arm (relative risk 0.59, 95% confidence interval 0.36 to 0.95; P=0.03; number needed to treat 13, 95% confidence interval 7 to 126).
Recurrent isolated distal deep vein thrombosis occurred in 16 (8%) patients in the rivaroxaban arm versus 31 (15%) in the placebo arm (P=0.02), whereas proximal deep vein thrombosis or pulmonary embolism occurred in seven (3%) versus eight (4%) patients (P=0.80).
No major bleeding events occurred in either group after randomisation during the active treatment phase.

Study Design

Type

RCT (n=402)

Blinding

Double-blind

Randomization

Computer-generated randomization list stratified by study centre with variable block size

Multicenter

Yes

Structured PICO

Does extending rivaroxaban treatment for an additional six weeks (total three months) reduce recurrent venous thromboembolism in adults with symptomatic isolated distal DVT compared to six weeks of treatment?

P

Population

402 adults (mean age 65 years, 58.5% female) across 28 centres in Italy with symptomatic isolated distal DVT without active cancer who completed an uneventful initial 6-week course of rivaroxaban, followed for 24 months.

I

Intervention

Rivaroxaban 20 mg once daily for an additional six weeks (total 3 months of treatment).

C

Comparator

Matching placebo once daily for an additional six weeks (both groups received standard dose rivaroxaban for the initial six weeks).

O

Outcome

Recurrent venous thromboembolism during follow-up after randomisation, defined as the composite of progression of isolated distal DVT, recurrent isolated distal DVT, proximal DVT, symptomatic pulmonary embolism, or fatal pulmonary embolism at 24 months follow-up, adjudicated by an independent committee.composite

Main Result

Relative Risk: 0.59 (95% CI 0.36–0.95)

Absolute Event Rate: 11% vs 19%

Number Needed to Treat: 13

p-value: p=0.03

Extending rivaroxaban treatment from six weeks to three months in patients with symptomatic isolated distal DVT significantly reduces the risk of recurrent VTE over two years without increasing major bleeding.

Limitations

Premature termination of enrolment before reaching the planned sample size of 1,100 patients due to slow recruitment and the COVID-19 pandemic
Potential overestimation of isolated distal DVT diagnosis and recurrence due to mandatory surveillance compression ultrasonography and inclusion of asymptomatic events
Observed benefit was mainly driven by reduction in recurrent isolated distal DVT rather than proximal DVT or pulmonary embolism
Findings do not apply to patients with cancer-associated isolated distal DVT, who were excluded from the trial

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Implication

Supports extending rivaroxaban to three months in isolated distal DVT; extends RCT evidence on optimal VTE treatment duration.

Abstract

OBJECTIVE: To compare two different treatment durations of rivaroxaban in patients with symptomatic isolated distal deep vein thrombosis (DVT). DESIGN: Randomised, double blind, placebo controlled clinical trial. SETTING: 28 outpatient clinics specialising in venous thromboembolism. PARTICIPANTS: 402 adults (≥18 years) with symptomatic isolated distal DVT. INTERVENTIONS: After receiving standard dose rivaroxaban for six weeks, participants were randomly assigned to receive rivaroxaban 20 mg or placebo once daily for an additional six weeks. Follow-up was for 24 months from study inclusion. MAIN OUTCOMES MEASURES: The primary efficacy outcome was recurrent venous thromboembolism during follow-up after randomisation, defined as the composite of progression of isolated distal DVT, recurrent isolated distal DVT, proximal DVT, symptomatic pulmonary embolism, or fatal pulmonary embolism. The primary safety outcome was major bleeding after randomisation until two days from the last dose of rivaroxaban or placebo. An independent committee adjudicated the outcomes. RESULTS: 200 adults were randomised to receive additional rivaroxaban treatment and 202 to receive placebo. Isolated distal DVT was unprovoked in 81 (40%) and 86 (43%) patients, respectively. The primary efficacy outcome occurred in 23 (11%) patients in the rivaroxaban arm and 39 (19%) in the placebo arm (relative risk 0.59, 95% confidence interval 0.36 to 0.95; P=0.03, number needed to treat 13, 95% confidence interval 7 to 126). Recurrent isolated distal DVT occurred in 16 (8%) patients in the rivaroxaban arm and 31 (15%) in the placebo arm (P=0.02). Proximal DVT or pulmonary embolism occurred in seven (3%) patients in the rivaroxaban arm and eight (4%) in the placebo arm (P=0.80). No major bleeding events occurred. CONCLUSIONS: Rivaroxaban administered for six additional weeks in patients with isolated distal DVT who had an uneventful six week treatment course reduces the risk of recurrent venous thromboembolism, mainly recurrent isolated distal DVT, over a two year follow-up without increasing the risk of haemorrhage. TRIAL REGISTRATION: EudraCT 2016-000958-36; ClinicalTrials.gov NCT02722447.

Discussion

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Cite This Study

Ageno et al. (2022) conducted an RCT in Symptomatic isolated distal deep vein thrombosis (DVT) (n=402). Rivaroxaban (extended 6-week course for a total of 3 months) vs. Placebo once daily for an additional 6 weeks (after initial 6 weeks of standard rivaroxaban) was evaluated on Recurrent venous thromboembolism (composite of progression of isolated distal DVT, recurrent isolated distal DVT, proximal DVT, symptomatic pulmonary embolism, or fatal pulmonary embolism) during 24-month follow-up (RR 0.59, 95% CI 0.36 to 0.95, p=0.03). Rivaroxaban for an additional six weeks reduced recurrent venous thromboembolism compared with placebo (11% vs 19%; RR 0.59, 95% CI 0.36-0.95; P=0.03) in isolated distal DVT.

synapsesocial.com/papers/6a7da8571b4d300315045408 https://doi.org/10.1136/bmj-2022-072623

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Rivaroxaban treatment for six weeks versus three months in patients with symptomatic isolated distal deep vein thrombosis: randomised controlled trial

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

Rivaroxaban treatment for six weeks versus three months in patients with symptomatic isolated distal deep vein thrombosis: randomised controlled trial

Figures

Key Points

Study Design

Structured PICO

Main Result

Limitations

Ask about this paper

Implication

Abstract

Discussion

Cite This Study

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