NCT02564718: Einstein Jr

Rivaroxaban for Treatment in Venous or Arterial Thrombosis in Neonates

Completed Phase 1, PHASE2 Results posted Last updated 10 July 2018

What this trial tests

Phase 1, PHASE2 trial testing Rivaroxaban (Xarelto, BAY59-7939) in Thromboembolism in 10 participants. Completed in 18 December 2017.

Timeline

19 November 2015

Primary endpoint
18 December 2017

18 December 2017

Quick facts

Lead sponsor	Bayer
Phase	Phase 1, PHASE2
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	other
Enrollment	10
Start date	19 November 2015
Primary completion	18 December 2017
Estimated completion	18 December 2017
Sites	9 locations across France, Italy, Austria, Israel, Germany, Turkey (Türkiye), Spain

Drugs / interventions tested

• Rivaroxaban (Xarelto, BAY59-7939) — full drug profile →

Conditions studied

• Thromboembolism — all drugs for Thromboembolism →

Sponsor

Bayer — full company profile →

Who can join

Under 6 Months, any sex, with Thromboembolism. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Day 1 Primary · 30 minutes to 1.5 hours post-dose; 2 to 4 hours post-dose (bid dosing) and 30 minutes to 3 hours post-dose; 7 to 8 hours post-dose on Day 1 (tid dosing)

Concentration of pharmacokinetic parameters of rivaroxaban in plasma was evaluated.

30 minutes to 1.5 hours post-dose

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Bid	85.2001	± 37.72

30 minutes to 3 hours post-dose

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Tid	42.6837	± 39.35

2 to 4 hours post-dose

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Bid	73.7641	± 64.38

7 to 8 hours post-dose

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Tid	12.1027	± 130.13

Number of Participants With Major and Clinically Relevant Non-Major Bleeding Events Secondary · From start of study drug administration until 30-day post study treatment period

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/deciliter (g/dL) or more, •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, example: 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

Major bleeding events

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Bid	0
Rivaroxaban (BAY59-7939) Suspension Tid	0

Clinically relevant non-major bleeding events

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Bid	0
Rivaroxaban (BAY59-7939) Suspension Tid	0

Number of Participants With Symptomatic Recurrent Venous Thromboembolism and Asymptomatic Deterioration in Thrombotic Burden on Repeat Imaging Secondary · From start of study drug administration until 30-day post study treatment period

Symptomatic recurrence of thromboembolism and asymptomatic deterioration was documented using the appropriate imaging test and confirmed by CIAC which was unaware of treatment assignment. Asymptomatic deterioration in thrombotic burden on repeat imaging, as assessed by the CIAC. Adjudication results were the basis for the final analyses.

Symptomatic recurrent venous thromboembolism

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Bid	0
Rivaroxaban (BAY59-7939) Suspension Tid	0

Asymptomatic deterioration in thrombotic burden

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Bid	0
Rivaroxaban (BAY59-7939) Suspension Tid	0

Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Day 3 Primary · 2 to 8 hours post-dose (bid dosing) and 30 minutes to 3 hours post-dose; 7 to 8 hours post-dose on Day 3 (tid dosing)

Concentration of pharmacokinetic parameters of rivaroxaban in plasma was evaluated.

30 minutes to 3 hours post-dose

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Tid	32.2879	± 267.05

2 to 8 hours post-dose

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Bid	102.3285	± 40.36

7 to 8 hours post-dose

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Tid	9.1716	± 160.52

Concentration of Rivaroxaban in Plasma as a Measure of Pharmacokinetics at Day 8 Primary · 10 to 16 hours post-dose on Day 8 (bid dosing)

Concentration of pharmacokinetic parameters of rivaroxaban in plasma was evaluated.

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Bid	2.5696	± 70.82
Rivaroxaban (BAY59-7939) Suspension Tid	NA	± NA

Change From Baseline in Prothrombin Time at Day 1 Primary · 10-16 hours post-dose on Day 8 (baseline), 2-4 hours after the first dose on Day 1 (bid dosing) and 7-8 hours after the first dose on Day 1 (tid dosing)

Prothrombin time is a global clotting test used for the assessment of the extrinsic pathway of the blood coagulation cascade.

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Bid	11.6	± 17.3
Rivaroxaban (BAY59-7939) Suspension Tid	0.025	± 0.714

Change From Baseline in Prothrombin Time at Day 3 Primary · 10-16 hours post-dose on Day 8 (baseline), 2-8 hours post-dose on Day 3 (bid dosing) and 0.5-3 hours post-dose on Day 3 (tid dosing)

Prothrombin time is a global clotting test used for the assessment of the extrinsic pathway of the blood coagulation cascade.

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Bid	3.74	± 2.84
Rivaroxaban (BAY59-7939) Suspension Tid	1.13	± 2.10

Change From Baseline in Activated Partial Thromboplastin Time (aPTT) at Day 1 Primary · 10-16 hours post-dose on Day 8 (baseline), 2-4 hours after the first dose on Day 1 (bid dosing) and 7-8 hours after the first dose on Day 1 (tid dosing)

The Activated partial thromboplastin time (aPTT) is a screening test for the intrinsic pathway and is sensitive for deficiencies of factors I, II, V, VIII, IX, X, XI and XII.

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Bid	13.6	± 12.4
Rivaroxaban (BAY59-7939) Suspension Tid	2.33	± 5.53

Change From Baseline in Activated Partial Thromboplastin Time (aPTT) at Day 3 Primary · 10-16 hours post-dose on Day 8 (baseline), 2-8 hours post-dose on Day 3 (bid dosing) and 0.5-3 hours post-dose on Day 3 (tid dosing)

The Activated partial thromboplastin time (aPTT) is a screening test for the intrinsic pathway and is sensitive for deficiencies of factors I, II, V, VIII, IX, X, XI and XII.

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Bid	7.02	± 5.08
Rivaroxaban (BAY59-7939) Suspension Tid	3.47	± 7.59

Anti-factor Xa Activity (Anti-Xa) Values at Day 1 Primary · 2-4 hours after the first dose on Day 1 (bid dosing) and 7-8 hours after the first dose on Day 1 (tid dosing)

The individual anti-Factor Xa activity was determined ex-vivo using a photometric method.

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Bid	63.3	± 60.8
Rivaroxaban (BAY59-7939) Suspension Tid	18.0	± 8.37

Anti-factor Xa Activity (Anti-Xa) Values at Day 3 Primary · 2-8 hours post-dose on Day 3 (bid dosing) and 0.5-3 hours post-dose on Day 3 (tid dosing)

The individual anti-Factor Xa activity was determined ex-vivo using a photometric method.

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Bid	67.3	± 48.7
Rivaroxaban (BAY59-7939) Suspension Tid	59.8	± 46.8

Anti-factor Xa Activity (Anti-Xa) Values at Day 8 Primary · 10-16 hours post-dose on Day 8 (both bid and tid dosing)

The individual anti-Factor Xa activity was determined ex-vivo using a photometric method.

Group	Value	95% CI
Rivaroxaban (BAY59-7939) Suspension Bid	7.25	± 0.00
Rivaroxaban (BAY59-7939) Suspension Tid	9.92	± 5.35

Adverse events — posted to ClinicalTrials.gov

Time frame: From start of study treatment up to 30 days after the last administration of study drug. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Rivaroxaban (BAY59-7939) Suspension Bid

Serious: 0/5 (0%)

Deaths: 0/5

Rivaroxaban (BAY59-7939) Suspension Tid

Serious: 1/5 (20%)

Deaths: 0/5

Serious adverse events (1 terms)

Reaction	System	Rivaroxaban (BAY59-7939) S…	Rivaroxaban (BAY59-7939) S…
Atrial thrombosis	Cardiac disorders	—	—

Other adverse events (1 terms — click to expand)

Reaction	System	Rivaroxaban (BAY59-7939) S…	Rivaroxaban (BAY59-7939) S…
Vomiting	Gastrointestinal disorders	—	—

Most-reported serious reactions: Atrial thrombosis.

Data from ClinicalTrials.gov NCT02564718 adverse events section.

Sponsor's own description

The purpose of this study is to find out whether rivaroxaban is safe and effective to use in children age newborn to less than 6 months and how long it stays in the body and how it is used in the body. Safety will be assessed by looking at the incidence and types of bleeding events. There will also be a check for worsening of blood clots.

Publications & conference data

3 peer-reviewed publications reference this trial (live from Europe PMC):

1. Bodyweight-adjusted rivaroxaban for children with venous thromboembolism (EINSTEIN-Jr): results from three multicentre, single-arm, phase 2 studies.
   Monagle P, Lensing AWA, Thelen K, Martinelli I, et al · · 2019 · cited 52× · PMID 31420317 · DOI 10.1016/s2352-3026(19)30161-9
2. Evidence Gaps in the Era of Non-Vitamin K Oral Anticoagulants.
   Aronis KN, Hylek EM. · · 2018 · cited 27× · PMID 29374049 · DOI 10.1161/jaha.117.007338
3. Adverse Events of Factor Xa Inhibitors in Pediatric Patients: A Meta-analysis and Pharmacovigilance Study.
   Chong S, Sun L, Mu G, Hua M, et al · · 2025 · PMID 39826085 · DOI 10.1007/s40272-024-00665-3