Cerebral Microbleeds During NOACs or Warfarin Therapy in NVAF Patients With Acute Ischemic Stroke (CMB-NOW)

NCT02356432 | Unknown DMC

• 1 other identifier: 14R-155
• Study Type: observational
• Target: 86
• Locations: 1 country
• Sites: 3

Brief Summary

Anticoagulants are generally recognized as a necessary therapy to prevent the recurrence of ischemic stroke in patients with non-valvular atrial fibrillation (NVAF), but in some patients they also cause bleedings, particularly intracranial hemorrhage. One of the independent predictors of intracerebral hemorrhage is the presence of cerebral microbleeds (CMBs); a high incidence of intracerebral hemorrhage is reported in patients with multiple CMBs. Recent study suggested that patients who had CMBs at baseline developed more new CMBs after 2 years (26%), compared with patients (12%) who did not have CMBs at baseline. However, there has been no study on the progression of CMBs in patients receiving so-called novel oral anticoagulants (NOACs). This study tests the hypothesis that the incidence of hemorrhagic stroke is lower in patients receiving NOACs (dabigatran, rivaroxaban, apixaban, and edoxaban) than in those receiving warfarin, and this difference reflects the difference in the effects of warfarin and NOACs on the progression of CMBs. Towards this goal, we enroll 200 patients with at least one CMB detected by 1.5 T MRI (T2\*WI) at baseline, who treated with NOACs or warfarin for 12 months. Primary endpoint is the proportion of subjects with an increased number of CMBs at Month 12 of treatment with NOACs or warfarin. If the results of this study support the efficacy of NOACs in preventing increase of CMBs, this would be of great interest to domestic and overseas clinicians, in view of the potential therapeutic impact, including that for primary prevention of ischemic stroke.

Conditions

Ischemic Stroke; Atrial Fibrillation Symptomatic

Keywords

non-valvular atrial fibrillation; cerebral microbleeds; warfarin; NOACs; acute ischemic stroke

Outcome Measures

Primary Outcomes (1)

• Proportion of subjects with an increased number of CMBs at Month 12 of treatment with NOACs or warfarin

  1 year

Secondary Outcomes (4)

• Proportion of subjects with an increased number of CMBs at Month 6 of treatment with NOACs or warfarin

  6 months

• The number of new CMBs in subjects with an increased number of CMBs at Months 6 and 12 of treatment with NOACs or warfarin

  1 year

• Location of CMBs (infratentorial, deep white matter, and lobar subgroups) in the NOACs and warfarin groups

  1 year

• Incidence rate of adverse events

  1 year

Study Arms (2)

NOACs group

Medication with dabigatran, rivaroxaban, apixaban, or edoxaban will not be assigned, but will be freely prescribed by each attending doctor based on assessment of the condition of each patient.

Warfarin group

Medication with warfarin: PT-INR should be controlled in accordance with the JCS2008 guideline concerning the drug treatment of atrial fibrillation, that is, INR 2.0 to 3.0 in patients younger than 70 years, or INR 1.6 to 2.6 in patients not younger than 70 years.

Eligibility Criteria

• Age: 20 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Patients with NVAF, who had at least one CMB at the time of entry into this study, and were prescribed a NOAC (dabigatran, rivaroxaban, apixaban, or edoxaban) or warfarin for secondary prevention of cerebral infarction or transient ischemic attack within 2 weeks after the onset. This study is an observational study, and the numbers of patients in the NOACs and warfarin groups were not predetermined, though the total number of patients for the study was limited to 200 for practical reasons.

You may qualify if:

• Diagnosis of NVAF
• Diagnosis of cerebral infarction or TIA within 2 weeks after onset
• Patients commenced on NOACs or warfarin therapy as a secondary prevention of cerebral infarction or transient ischemic attack, whether or not anticoagulation therapy was used before enrollment in this study
• Age ≥20 years and ≤85 years
• Ability to give valid consent and to provide consent in writing or availability of relatives to provide surrogate consent.
• At least one CMB detected by 1.5 T MRI (T2\*WI) before enrollment in this study

You may not qualify if:

• Patients using aspirin or other antiplatelet agents concomitantly
• Patients in whom NOAC or warfarin is contraindicated
• Patients with renal dysfunction (CrCL \<15 mL/min)
• Patients with uncontrollable hypertension
• Patients who are otherwise ineligible to take part in this study as judged by the study doctor

Sponsors & Collaborators

• Tokai University: lead
• Daiichi Sankyo: collaborator

Study Sites (3)

St. Marianna University School of Medicine Hospital

Kawasaki, Kanagawa, 216-8511, Japan

Location

Kitasato University Hospital

Sagamihara, Kanagawa, 252-0373, Japan

Location

Yokohama City University Hospital

Yokohama, Kanagawa, 236-0004, Japan

Location

Related Publications (1)

• Takizawa S, Tanaka F, Nishiyama K, Hasegawa Y, Nagata E, Mizuma A, Yutani S, Nakayama T, Kobayashi H, Yanagimachi N, Okazaki T, Kitagawa K; CMB-NOW Study Investigators. Protocol for Cerebral Microbleeds during the Non-Vitamin K Antagonist Oral Anticoagulants or Warfarin Therapy in Stroke Patients with Nonvalvular Atrial Fibrillation (CMB-NOW) Study: Multisite Pilot Trial. J Stroke Cerebrovasc Dis. 2015 Sep;24(9):2143-8. doi: 10.1016/j.jstrokecerebrovasdis.2015.05.032. Epub 2015 Jul 4.

  PMID: 26153510 DERIVED

MeSH Terms

Conditions

Ischemic Stroke

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases

Study Officials

• Shunya Takizawa, MD, PhD

  Tokai University School of Medicine

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Target Duration: 1 Year
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor, Division of Neurology, Department of Internal Medicine, Tokai University School of Medicine

Study Record Dates

• First Submitted: February 1, 2015
• First Posted: February 5, 2015
• Study Start: March 1, 2015
• Primary Completion: September 1, 2016
• Study Completion: September 1, 2017
• Last Updated: October 20, 2016

Record last verified: 2016-10

Locations

JP (3)