EINSTEIN Junior: Oral Rivaroxaban in Children With Venous Thrombosis

Study at a glance

From the registry record, last updated by the sponsor on 1 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title

Multicenter, Open-label, Active-controlled, Randomized Study to Evaluate the Efficacy and Safety of an age-and Body Weight-adjusted Rivaroxaban Regimen Compared to Standard of Care in Children With Acute Venous Thromboembolism

ClinicalTrials.gov ID

NCT02234843

Acronym / sponsor ID

EINSTEIN Jr / 14372

Conditions

Venous Thromboembolism

Keywords

Pediatric

Phase

Phase 3

Study type

Interventional

Recruitment status

Completed

Enrolment

500 participants (actual)

Lead sponsor

BayerIndustry (pharma, biotech, devices)

Collaborators

Janssen Research & Development, LLC

Study start

13 Nov 2014 (actual)

Primary completion

30 Jan 2019 (actual)

Study completion

30 Jan 2019 (actual)

First posted

9 Sep 2014 (estimated)

Results

Posted 1 Apr 2020

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Study design

Primary purpose

Treatment

Allocation

Randomised

Intervention model

Parallel groups

Masking

None (open label)

Number of arms

2

Who may qualify

Ages

Up to 17 years

Sex

All

Healthy volunteers

Not accepted

Age groups

Child

Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.

Interventions

Primary outcome

1. Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period

   Time frame: During the main study treatment period (i.e., 3 months, except for children with central venous catheter venous thromboembolism (CVC-VTE) aged <2 years for whom it was 1 month)

   The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference population

2. Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During the Main Treatment Period

   Time frame: During the main study treatment period (i.e., 3 months, except for children with CVC-VTE aged <2 years for whom it was 1 month)

   The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference population

3. Incidence Rates of All Symptomatic Recurrent Venous Thromboembolism During Extended Treatment Period

   Time frame: During extended treatment period: up to month 12.

   Incidence rates for all children except those aged < 2 years with catheter-related thrombosis. If no participant in the specific subgroup entered in the specific optional extension period, no analysis of an outcome was possible., The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Incidence = number of events / number at risk, where: number of events = number of subjects having the event in the time window. number at risk = number of subjects in reference Population.

4. Number of Subjects With the Composite of All Symptomatic Recurrent Venous Thromboembolism During the 30 Days Post-study Treatment Period (i.e. >2 and ≤ 30 Days After Stop of Study Medication)

   Time frame: More than 2 and up to 30 days after stop of study medication

   The Central independent adjudication committee (CIAC) classified symptomatic recurrent venous thromboembolism (VTE). Age group with primary efficacy outcome was reported.

5. Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Main Treatment Period

   Time frame: During the main study treatment period (i.e., 3 months, except for children with CVC-VTE aged <2 years for whom it was 1 month)

   The Central independent adjudication committee (CIAC) classified bleeding as: Major bleeding defined as overt bleeding and: · associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults, or occurring in a critical site, e.g. intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, retroperitoneal, or contributing to death. Clinically relevant non-major bleeding defined as overt bleeding not meeting the criteria for major bleeding, but associated with: medical intervention, or unscheduled contact (visit or telephone call) with a physician, or (temporary) cessation of study treatment, or discomfort for the child such as pain or impairment of activities of daily life (such as loss of school days or hospitalization).

6. Incidence Rates of the Composite of Treatment Emergent Overt Major Bleeding and Clinically Relevant Non-major (CRNM) Bleeding During Extended Treatment Period

   Time frame: During extended treatment period: up to month 12.

   Incidence rates for all children except those aged < 2 years with catheter-related thrombosis. If no participant entered in the specific optional extension period, no analysis of an outcome was possible. The CIAC classified bleeding as: Major bleeding defined as overt bleeding and: associated with a fall in hemoglobin of 2 g/dL or more, or leading to a transfusion of the equivalent of 2 or more units of packed red blood cells or whole blood in adults, or occurring in a critical site, e.g. intracranial, intraspinal, intraocular, pericardial, intraarticular, intramuscular with compartment syndrome, retroperitoneal, or contributing to death. Clinically relevant non-major bleeding defined as overt bleeding not meeting the criteria for major bleeding, but associated with: medical intervention, or unscheduled contact with a physician, or (temporary) cessation of study treatment, or discomfort for the child such as pain or impairment of activities of daily life.

Results and safety

Loading the posted results from ClinicalTrials.gov…

Research links

• Official record on ClinicalTrials.govLast updated by the sponsor 1 Apr 2020.
• Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
• Derived from this study: PubMed 36006613Palumbo JS, Lensing AWA, Brandao LR, Hooimeijer HL, Kenet G, van Ommen H, Pap AF, Majumder M, Kubitza D, Thelen K, Willmann S, Prins MH, Monagle P, Male C. Anticoagulation in pediatric cancer-associated venous thromboembolism: a subgroup analysis of EINSTEIN-Jr. Blood Adv. 2022 Nov 22;6(22):5821-5828. doi: 10.1182/bloodadvances.2022008160.
• Derived from this study: PubMed 33351120Connor P, Sanchez van Kammen M, Lensing AWA, Chalmers E, Kallay K, Hege K, Simioni P, Biss T, Bajolle F, Bonnet D, Grunt S, Kumar R, Lvova O, Bhat R, Van Damme A, Palumbo J, Santamaria A, Saracco P, Payne J, Baird S, Godder K, Labarque V, Male C, Martinelli I, Morales Soto M, Motwani J, Shah S, Hooimeijer HL, Prins MH, Kubitza D, Smith WT, Berkowitz SD, Pap AF, Majumder M, Monagle P, Coutinho JM. Safety and efficacy of rivaroxaban in pediatric cerebral venous thrombosis (EINSTEIN-Jr CVT). Blood Adv. 2020 Dec 22;4(24):6250-6258. doi: 10.1182/bloodadvances.2020003244.
• Derived from this study: PubMed 33002131Thom K, Lensing AWA, Nurmeev I, Bajolle F, Bonnet D, Kenet G, Massicotte MP, Karakas Z, Palumbo JS, Saracco P, Amedro P, Chain J, Chan AK, Ikeyama T, Lam JCM, Gauger C, Pap AF, Majumder M, Kubitza D, Smith WT, Berkowitz SD, Prins MH, Monagle P, Young G, Male C. Safety and efficacy of anticoagulant therapy in pediatric catheter-related venous thrombosis (EINSTEIN-Jr CVC-VTE). Blood Adv. 2020 Oct 13;4(19):4632-4639. doi: 10.1182/bloodadvances.2020002637.
• Derived from this study: PubMed 31699660Male C, Lensing AWA, Palumbo JS, Kumar R, Nurmeev I, Hege K, Bonnet D, Connor P, Hooimeijer HL, Torres M, Chan AKC, Kenet G, Holzhauer S, Santamaria A, Amedro P, Chalmers E, Simioni P, Bhat RV, Yee DL, Lvova O, Beyer-Westendorf J, Biss TT, Martinelli I, Saracco P, Peters M, Kallay K, Gauger CA, Massicotte MP, Young G, Pap AF, Majumder M, Smith WT, Heubach JF, Berkowitz SD, Thelen K, Kubitza D, Crowther M, Prins MH, Monagle P; EINSTEIN-Jr Phase 3 Investigators. Rivaroxaban compared with standard anticoagulants for the treatment of acute venous thromboembolism in children: a randomised, controlled, phase 3 trial. Lancet Haematol. 2020 Jan;7(1):e18-e27. doi: 10.1016/S2352-3026(19)30219-4. Epub 2019 Nov 5.
• Derived from this study: PubMed 31420317Monagle P, Lensing AWA, Thelen K, Martinelli I, Male C, Santamaria A, Samochatova E, Kumar R, Holzhauer S, Saracco P, Simioni P, Robertson J, Grangl G, Halton J, Connor P, Young G, Molinari AC, Nowak-Gottl U, Kenet G, Kapsa S, Willmann S, Pap AF, Becka M, Twomey T, Beyer-Westendorf J, Prins MH, Kubitza D; EINSTEIN-Jr Phase 2 Investigators. Bodyweight-adjusted rivaroxaban for children with venous thromboembolism (EINSTEIN-Jr): results from three multicentre, single-arm, phase 2 studies. Lancet Haematol. 2019 Oct;6(10):e500-e509. doi: 10.1016/S2352-3026(19)30161-9. Epub 2019 Aug 13.
• Derived from this study: PubMed 30598642Lensing AWA, Male C, Young G, Kubitza D, Kenet G, Patricia Massicotte M, Chan A, Molinari AC, Nowak-Goettl U, Pap AF, Adalbo I, Smith WT, Mason A, Thelen K, Berkowitz SD, Crowther M, Schmidt S, Price V, Prins MH, Monagle P. Rivaroxaban versus standard anticoagulation for acute venous thromboembolism in childhood. Design of the EINSTEIN-Jr phase III study. Thromb J. 2018 Dec 21;16:34. doi: 10.1186/s12959-018-0188-y. eCollection 2018.

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Referral and contact

AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.

109 sites in 28 countries: see every site and its status.