Trial Outcomes & Findings for Rivaroxaban Versus Warfarin in Acute Ischemic Stroke With Atrial Fibrillation (NCT NCT02042534)

NCT ID: NCT02042534

Last Updated: 2017-02-08

Results Overview

Intracranial bleeding: symptomatic hemorrhage confirmed by CT or MRI or asymptomatic hemorrhage on follow-up GRE or SWI imaging at 1 month Recurrent ischemic lesion: symptomatic ischemic stroke confirmed by relevant neuroimagings or asymptomatic recurrent ischemic lesion on follow-up or FLAIR imaging at 1 month

Recruitment status

COMPLETED

Study phase

PHASE2

Target enrollment

195 participants

Primary outcome timeframe

1 month after randomization

Results posted on

2017-02-08

Participant Flow

Participant milestones

Participant milestones
Measure	Rivaroxaban Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days. Rivaroxaban: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min. The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.	Warfarin Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 \[2.0 - 3.0\]. Warfarin: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.
Overall Study STARTED	101	94
Overall Study COMPLETED	101	94
Overall Study NOT COMPLETED	0	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Rivaroxaban Versus Warfarin in Acute Ischemic Stroke With Atrial Fibrillation

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Rivaroxaban n=95 Participants Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days. Rivaroxaban: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min. The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.	Warfarin n=88 Participants Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 \[2.0 - 3.0\]. Warfarin: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.	Total n=183 Participants Total of all reporting groups
Age, Continuous	70.2 years STANDARD_DEVIATION 10.1 • n=99 Participants	70.6 years STANDARD_DEVIATION 10.9 • n=107 Participants	70.4 years STANDARD_DEVIATION 10.4 • n=206 Participants
Gender Female	40 Participants n=99 Participants	36 Participants n=107 Participants	76 Participants n=206 Participants
Gender Male	55 Participants n=99 Participants	52 Participants n=107 Participants	107 Participants n=206 Participants
Body Mass Index	24.4 kg/㎡ STANDARD_DEVIATION 3.3 • n=99 Participants	23.6 kg/㎡ STANDARD_DEVIATION 3.1 • n=107 Participants	24.0 kg/㎡ STANDARD_DEVIATION 3.2 • n=206 Participants

PRIMARY outcome

Timeframe: 1 month after randomization

Population: * modified Intention to treat: 95 / 88 (Rivaroxaban/Warfarin) * Per protocol: 93 / 87 (Rivaroxaban/Warfarin) * Safety: 98 / 90 (Rivaroxaban/Warfarin)

Outcome measures

Outcome measures
Measure	Rivaroxaban n=95 Participants Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days. Rivaroxaban: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min. The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.	Warfarin n=88 Participants Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 \[2.0 - 3.0\]. Warfarin: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.
Number of Participants With Intracranial Bleeding and/or Recurrent Ischemic Lesion as Confirmed by MRI Imaging	47 Participants	48 Participants

SECONDARY outcome

Timeframe: at 1 month

Population: Modified ITT

Intracranial bleeding confirmed by relevant neuroimagings

Outcome measures

Outcome measures
Measure	Rivaroxaban n=95 Participants Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days. Rivaroxaban: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min. The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.	Warfarin n=88 Participants Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 \[2.0 - 3.0\]. Warfarin: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.
The Number of Patients With Intracranial Bleeding	30 Participants	25 Participants

SECONDARY outcome

Timeframe: at 1 month

Population: Modified ITT

Recurrent ischemic lesion confirmed by relevant neuroimagings

Outcome measures

Outcome measures
Measure	Rivaroxaban n=98 Participants Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days. Rivaroxaban: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min. The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.	Warfarin n=88 Participants Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 \[2.0 - 3.0\]. Warfarin: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.
The Number of Patients With Recurrent Ischemic Lesion	28 Participants	31 Participants

SECONDARY outcome

Timeframe: at 1month

Time to event will be calculated

Outcome measures

Outcome measures
Measure	Rivaroxaban n=94 Participants Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days. Rivaroxaban: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min. The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.	Warfarin n=88 Participants Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 \[2.0 - 3.0\]. Warfarin: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.
Length of Hospitalization	4.6 days Standard Deviation 3.9	5.6 days Standard Deviation 4.3

SECONDARY outcome

Timeframe: at 1 month

Population: Modified ITT (mRS 0,1 at Week 4, n(%)

modified Rankin Score 0 : No symptoms at all 1. : No significant disability despite symptoms; able to carry out all usual duties and activities 2. : Slight disability; unable to carry out all previous activities, but able to look after own affairs without assistance 3. : Moderate disability; requiring some help, but able to walk without assistance 4. : Moderately severe disability; unable to walk without assistance and unable to attend to own bodily needs without assistance 5. : Severe disability; bedridden, incontinent and requiring constant nursing care and attention 6. : Dead

Outcome measures

Outcome measures
Measure	Rivaroxaban n=95 Participants Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days. Rivaroxaban: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min. The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.	Warfarin n=88 Participants Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 \[2.0 - 3.0\]. Warfarin: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.
Number of Participants With Modified Rankin Score of 0 or 1 at Week 4	79 participants	64 participants

Adverse Events

Rivaroxaban

Serious events: 6 serious events

Other events: 46 other events

Deaths: 0 deaths

Warfarin

Serious events: 5 serious events

Other events: 51 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Rivaroxaban n=98 participants at risk Safety population : 98 (patients) Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days. Rivaroxaban: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min. The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.	Warfarin n=90 participants at risk Safety population : 90 (patients) Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 \[2.0 - 3.0\]. Warfarin: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.
Ear and labyrinth disorders Vertigo positional	0.00% 0/98	1.1% 1/90 • Number of events 1
Cardiac disorders Atrial fibrillation	1.0% 1/98 • Number of events 1	0.00% 0/90
Gastrointestinal disorders Gastrooesophageal reflux disease	1.0% 1/98 • Number of events 1	0.00% 0/90
Gastrointestinal disorders Large intestine polyp	1.0% 1/98 • Number of events 1	0.00% 0/90
Investigations International normalised ratio increased	1.0% 1/98 • Number of events 1	0.00% 0/90
Investigations Laboratory test abnormal	0.00% 0/98	1.1% 1/90 • Number of events 1
Musculoskeletal and connective tissue disorders Arthritis	0.00% 0/98	1.1% 1/90 • Number of events 1
Nervous system disorders Cerebral infarction	1.0% 1/98 • Number of events 1	1.1% 1/90 • Number of events 1
Nervous system disorders Stroke in evolution	1.0% 1/98 • Number of events 1	0.00% 0/90
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/98	1.1% 1/90 • Number of events 1

Other adverse events

Other adverse events
Measure	Rivaroxaban n=98 participants at risk Safety population : 98 (patients) Rivaroxaban group for 1 month : initial 5 days after randomization rivaroxaban 10mg QD will be administered. Rivaroxaban 20mg QD, but 15mg in case of Cr CL will be administered for remaining 25 days. Rivaroxaban: Rivaroxaban group receive oral rivaroxaban 10 mg once daily for 5 consecutive days, followed by 20 mg or 15 mg in patients with a calculated creatinine clearance of 30-49 ml/min. The dosage of rivaroxaban is leveraged from results of ROCKET-AF trial, where 20 mg of rivaroxaban was shown to offer balanced efficacy and safety.	Warfarin n=90 participants at risk Safety population : 90 (patients) Patients allocated to warfarin receive warfarin plus aspirin 100mg until INR value exceed 1.7 followed by warfarin monotherapy with target INR value of 2.5 \[2.0 - 3.0\]. Warfarin: To harmonize the warfarin regimen across the sites, fixed algorithm was used in dose calculation, both loading and maintenance, and age, sex, ethnicity, race, weight, height, smoking history, presence of liver disease, indication, baseline INR, target INR and concomitant medication were considered as cofactors (http://www.warfarindosing.org/Source/InitialDose.aspx). Investigators will manage anticoagulation with warfarin per routine clinical care.
Blood and lymphatic system disorders Anaemia	2.0% 2/98 • Number of events 2	0.00% 0/90
Gastrointestinal disorders Constipation	4.1% 4/98 • Number of events 4	6.7% 6/90 • Number of events 6
Gastrointestinal disorders Nausea	3.1% 3/98 • Number of events 3	1.1% 1/90 • Number of events 1
Infections and infestations Nasopharyngitis	0.00% 0/98	2.2% 2/90 • Number of events 2
Investigations International normalised ratio increased	1.0% 1/98 • Number of events 1	6.7% 6/90 • Number of events 6
Metabolism and nutrition disorders Decreased appetite	0.00% 0/98	3.3% 3/90 • Number of events 3
Musculoskeletal and connective tissue disorders Musculoskeletal pain	2.0% 2/98 • Number of events 2	4.4% 4/90 • Number of events 5
Nervous system disorders Dizziness	3.1% 3/98 • Number of events 3	8.9% 8/90 • Number of events 9
Psychiatric disorders Delirium	0.00% 0/98	2.2% 2/90 • Number of events 2
Psychiatric disorders Depression	1.0% 1/98 • Number of events 1	3.3% 3/90 • Number of events 3
Psychiatric disorders Insomnia	1.0% 1/98 • Number of events 1	2.2% 2/90 • Number of events 2
Vascular disorders Hypertension	4.1% 4/98 • Number of events 5	0.00% 0/90
Vascular disorders Hypotension	1.0% 1/98 • Number of events 1	2.2% 2/90 • Number of events 2
Social circumstances Others	24.5% 24/98 • Number of events 68	13.3% 12/90 • Number of events 103

Additional Information

Sun U. Kwon, MD, PhD, Prof

Asan Medical Center, University of Ulsan

Phone: 82-2-3010-3960

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place