Oral Rivaroxaban in Children With Venous Thrombosis

NCT01684423 | Completed Phase 2 Results DMC FDA Drug

• 2 other identifiers: 143732011-004539-30
• Study Type: interventional
• Target: 64
• Locations: 9 countries
• Sites: 55

Brief Summary

The purpose of this study is to find out whether rivaroxaban is safe to use in children and how long it stays in the body. There will also be a check for bleeding and worsening of blood clots.

Conditions

Venous Thrombosis

Outcome Measures

Primary Outcomes (1)

• Number of Subjects With Major and Clinically Relevant Non-Major Bleeding Events

  Central independent adjudication committee (CIAC) classified bleeding as follows: Major bleeding is defined as overt bleeding and: * associated with a fall in hemoglobin of 2 gram/decilitre (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, intra-articular, intramuscular with compartment syndrome, retroperitoneal, or * contributing to death. Clinically relevant non-major bleeding is 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 * cessation (temporary) 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).

  From start of study drug administration until end of the 30-day treatment period

Secondary Outcomes (6)

• Number of Subjects With Symptomatic Recurrent Venous Thromboembolism

  From start of study drug administration until end of the 30-day treatment period

• Number of Subjects With Asymptomatic Deterioration in Thrombotic Burden

  Repeat imaging at the end of the 30 day treatment period

• Change From Baseline in Prothrombin Time at Specified Time Points

  0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31

• Change From Baseline in Activated Partial Thromboplastin Time at Specified Time Points

  0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31

• Anti-factor Xa Values at Specified Time Points

  0 hours (pre-dose) to 8 hours post-dose on Day 15 and 24 hours post-dose on Day 31

Study Arms (5)

Rivaroxaban (BAY59-7939) tablet, OD, Age: 12 - <18

EXPERIMENTAL

Subjects aged from 12 - \<18 years were administered with age and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) IR (immediate-release) tablet once daily (OD) under fed conditions for 30 days. Subjects with a body weight of 14 to less than 50 kilogram (kg) received a dose (equivalent to 20 milligram \[mg\] in adults) ranging from 5 to 15 mg, and subjects with a body weight (comparable to adults) of greater than or equal to 50 kg received a dose of 20 mg.

Drug: Rivaroxaban (Xarelto, BAY59-7939)

Comparator, Age: 12 - <18 years

ACTIVE COMPARATOR

Subjects aged from 12 - \<18 years received comparator as per standard of care. The dosage given was to be adjusted based on the individual body weight (low molecular weight heparin, fondaparinux) or international normalized ratio (INR) adjusted (vitamin K antagonist).

Drug: Active comparator

Rivaroxaban (BAY59-7939) tablet, OD, Age: 6 - <12 years

EXPERIMENTAL

Subjects aged from 6 - \<12 years were administered with age- and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) IR tablet once daily under fed conditions for 30 days. Subjects with a body weight of 14 to less than 50 kg received a dose (equivalent to 20 mg in adults) ranging from 5 to 15 mg, and subjects with a body weight (comparable to adults) of greater than or equal to 50 kg received a dose of 20 mg.

Drug: Rivaroxaban (Xarelto, BAY59-7939)

Rivaroxaban (BAY59-7939) suspension, BID, Age: 6 - <12 years

EXPERIMENTAL

Subjects aged from 6 - \<12 years were administered with age- and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) suspension under fed conditions twice daily (BID). Subjects with a body weight of 9 to less than 50 kg received a total daily dose (equivalent to 20 mg in adults) ranging from 6.4 to 15 mg and subjects with a body weight of greater than or equal to 50 kg received a total daily dose of 20 mg.

Drug: Rivaroxaban (BAY59-7939) suspension

Comparator, Age: 6 - <12 years

ACTIVE COMPARATOR

Subjects aged from 6 - \<12 years received comparator as per standard of care. The dosage given was to be adjusted based on the individual body weight (low molecular weight heparin, fondaparinux) or INR-adjusted (vitamin K antagonist).

Drug: Active comparator

Interventions

Rivaroxaban (Xarelto, BAY59-7939) DRUG

Subjects were administered with age- and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) IR tablet once daily under fed conditions for 30 days.

Rivaroxaban (BAY59-7939) tablet, OD, Age: 12 - <18; Rivaroxaban (BAY59-7939) tablet, OD, Age: 6 - <12 years

Active comparator DRUG

Subjects received comparator as per standard of care. The dosage given was to be adjusted based on the individual body weight (low molecular weight heparin, fondaparinux) or international normalized ratio (INR) adjusted (vitamin K antagonist).

Comparator, Age: 12 - <18 years; Comparator, Age: 6 - <12 years

Rivaroxaban (BAY59-7939) suspension DRUG

Subjects aged were administered with age- and body weight-adjusted oral dose of rivaroxaban (BAY59-7939) suspension under fed conditions twice daily.

Rivaroxaban (BAY59-7939) suspension, BID, Age: 6 - <12 years

Eligibility Criteria

• Age: 6 Years - 17 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Children aged 6 to \< 18 years with documented symptomatic or asymptomatic venous thrombosis treated for at least 2 months or, in case of catheter related thrombosis, treated for at least 6 weeks with LMWH (low molecular weight heparin), , fondaparinux and/or VKA (vitamin K antagonist).
• Informed consent provided and, if applicable, child assent provided

You may not qualify if:

• Active bleeding or high risk for bleeding contraindicating anticoagulant therapy
• Symptomatic progression of venous thrombosis during preceding anticoagulant treatment
• Planned invasive procedures, including lumbar puncture and removal of non peripherally placed central lines during study treatment
• An estimated glomerular filtration rate (eGFR) \< 30 mL/min/1.73 m2
• Hepatic disease which is associated with coagulopathy leading to a clinically relevant bleeding risk or ALT \> 5x upper level of normal (ULN) or total bilirubin \> 2x ULN with direct bilirubin \> 20% of the total
• Platelet count \< 50 x 10\^9/L
• Hypertension defined as \> 95th age percentile
• Life expectancy \< 3 months
• Concomitant use of strong inhibitors of both cytochrome P450 isoenzyme 3A4 (CYP3A4) and P-glycoprotein (P-gp), i.e. all human immunodeficiency virus protease inhibitors and the following azole antimycotics agents: ketoconazole, itraconazole, voriconazole, posaconazole, if used systemically
• Concomitant use of strong inducers of CYP3A4, i.e. rifampicin, rifabutin, phenobarbital, phenytoin and carbamazepine

Sponsors & Collaborators

• Bayer: lead
• Janssen Research & Development, LLC: collaborator

Study Sites (59)

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Little Rock, Arkansas, 72202-3500, United States

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Los Angeles, California, 90027-6089, United States

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Orange, California, 92868-3974, United States

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Chicago, Illinois, 60611, United States

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Indianapolis, Indiana, 46202, United States

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Detroit, Michigan, 48201-2196, United States

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Minneapolis, Minnesota, 55404, United States

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New Hyde Park, New York, 11040, United States

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Cleveland, Ohio, 44106-2602, United States

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Columbus, Ohio, 43205-2696, United States

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Philadelphia, Pennsylvania, 19104, United States

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Houston, Texas, 77030, United States

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Richmond, Virginia, 23298, United States

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Westmead, New South Wales, 2145, Australia

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Parkville, Victoria, 3052, Australia

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South Brisbane, 4101, Australia

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Graz, Styria, 8036, Austria

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Innsbruck, Tyrol, 6020, Austria

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Linz, Upper Austria, 4020, Austria

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Vienna, 1090, Austria

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Edmonton, Alberta, T6G 2B7, Canada

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Hamilton, Ontario, L8N 3Z5, Canada

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Ottawa, Ontario, K1H 8L1, Canada

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Toronto, Ontario, M5G 1X8, Canada

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Québec, G1V 4G2, Canada

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Bordeaux, 33076, France

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Montpellier, 34295, France

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Nantes, 44093, France

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Paris, 75015, France

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Paris, 75019, France

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Rennes, 35033, France

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Toulouse, 31059, France

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Freiburg im Breisgau, Baden-Wurttemberg, 79106, Germany

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Erlangen, Bavaria, 91054, Germany

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Frankfurt am Main, Hesse, 60590, Germany

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Dresden, Saxony, 01307, Germany

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Lübeck, Schleswig-Holstein, 23538, Germany

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Berlin, 13353, Germany

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Beersheba, 8410101, Israel

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Haifa, 3109601, Israel

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Jerusalem, 9112001, Israel

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Petah Tikva, 4920235, Israel

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Ramat Gan, 5262000, Israel

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Bari, Apulia, 70124, Italy

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Genoa, Liguria, 16147, Italy

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Milan, Lombardy, 20122, Italy

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Pavia, Lombardy, 27100, Italy

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Turin, Piedmont, 10126, Italy

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Padua, Veneto, 35128, Italy

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Amsterdam, 1081 HV, Netherlands

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Amsterdam, Netherlands

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Nijmegen, 6525 GA, Netherlands

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Rotterdam, 3015 GJ, Netherlands

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Utrecht, 3584 CX, Netherlands

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Basel, Canton of Basel-City, 4056, Switzerland

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Sankt Gallen, Canton of St. Gallen, 9006, Switzerland

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Bern, 3010, Switzerland

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Lucerne, 6000, Switzerland

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Zurich, 8032, Switzerland

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Related Links

• Click here to find information about studies related to Bayer Healthcare products conducted in Europe

MeSH Terms

Conditions

Venous Thrombosis

Interventions

Rivaroxaban; Suspensions

Condition Hierarchy (Ancestors)

Thrombosis; Embolism and Thrombosis; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Thiophenes; Sulfur Compounds; Organic Chemicals; Morpholines; Oxazines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Colloids; Complex Mixtures; Dosage Forms; Pharmaceutical Preparations

Results Point of Contact

• Title: Therapeutic Area Head
• Organization: BAYER

clinical-trials-contact@bayer.com

Study Officials

• Bayer Study Director

  Bayer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: GT60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: NON RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 11, 2012
• First Posted: September 13, 2012
• Study Start: February 19, 2013
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2016
• Last Updated: September 21, 2017
• Results First Posted: September 21, 2017

Record last verified: 2017-08

Locations

CA (5); FR (7); AU (3); DE (6); US (13); NL (5); CH (5); IL (5); IT (6)