Clinical trial NCT02159287: Study of the Efficacy, Safety and Tolerability of Low Molecular Weight Heparin vs. Unfractionated Heparin in Stroke
Official title: Study of the Efficacy, Safety and Tolerability of Low Molecular Weight Heparin vs. Unfractionated Heparin as Bridging Therapy in Patients With Embolic Stroke Due to Atrial Fibrillation
Study type: INTERVENTIONAL
Overall status: UNKNOWN
Phase: PHASE2
Conditions: Embolic Stroke
Keywords: ischemic stroke
atrial fibrillation
bridging therapy
Lead sponsor: Shiraz University of Medical Sciences
Sponsor class: OTHER
First posted: 2014-06-09
Enrollment: 80
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: Patients with Atrial fibrillation (AF) make a unique group of ischemic stroke, mostly caused by emboli from the left atrial appendage. Oral anticoagulation (Warfarin) is recommended for prevention of recurrent embolic stroke but it takes several days to reach a therapeutic international normalized ratio (INR : 2.5) so bridging therapy with a short acting intravenous anticoagulant is recommended until therapeutic INR level is reached. A common strategy is to use intravenous unfractionated heparin (UFH) until a standard activated partial thromboplastin time (aPTT) is reached and then initiating warfarin. Another strategy is to use subcutaneous (SQ) injection of a low-molecular-weight heparin (LMWH) eg. Enoxaparin.

The investigators will compare LMWH and UFH, focusing on risk of new stroke and mortality rate.

METHOD: This study is randomized controlled trial that will be performed in 80 patients ages between 18 and 75 with confirmed acute ischemic stroke purely due to AF who will be hospitalized in Shiraz Medical University affiliated teaching hospitals. Patients will be randomly assigned in two groups. A brain CT will be done to confirm the absence of intracranial hemorrhage and to assess the size of cerebral ischemia.

First group will receive 1 mg of enoxaparin (Clexane, Sanofi, Paris) per kilogram of body weight SQ every 12 hour with warfarin 5mg orally everyday and both drugs will be continued until the target INR level (2.5) is reached then clexane will be discontinued.

The second group will receive continuous UFH infusion 1000 unit per hour and then the dose will be adjusted to maintain a therapeutic aPTT (two times to baseline) level then warfarin will be started (5 mg everyday).

The investigators will follow patients in both groups until target INR will be achieved (2.5) and after that clexane and UFH will be discontinued. Adverse events will be assessed in both groups for three months.

Data will be analyzed with Statistical Package for the Social Sciences (SPSS) version 15 and Chi-square statistics.

Main outcome of our study will be evaluation of new stroke, mortality, central nervous system (CNS) hemorrhage, major bleeding, drop out and other unwanted side effects in first week and three months after stroke.


Eligibility criteria: Inclusion Criteria:

* confirmed diagnosis of acute ischemic stroke purely due to AF
* AF confirmed by ECG or 24 hour holter monitoring
* patients who need initiation of anticoagulation for prevention of recurrent stroke

Exclusion Criteria:

* ages less than 18 or more than 75
* no cooperation
* CNS hemorrhage
* major bleeding
* infarction size of more than one third of middle cerebral artery territory
* National Institutes of Health Stroke Scale (NIHSS) more than 20
* hypersensitivity to IV UFH or LMWH
* no informed consent
* other causes for stroke except AF
* pregnancy
* breast feeding
* uncontrolled hypertension (BP more than 220/120)
* renal, hepatic, respiratory or cardiac failure
* myocardial infarction
* infectious endocarditis
* coma
* vasculitis
* dissection

Primary outcomes:
measure: mortality
timeFrame: up to the 3 months of follow-up
measure: ischemic stroke
timeFrame: up to the 3 months of follow-up
measure: hemorrhagic stroke
timeFrame: up to the 3 months of follow-up
Secondary outcomes:
measure: symptomatic CNS hemorrhage
timeFrame: up to the 3 months of follow-up
measure: Non-CNS hemorrhage
timeFrame: up to the 3 months of follow-up
measure: asymptomatic CNS_hemorrhage
timeFrame: up to the 3 months of follow-up
measure: time to reach target INR
timeFrame: average time 7 to 10 days (it is variable between individuals)
measure: tolerability of drugs
timeFrame: participants will be followed for the duration of hospital stay, an expected average of 1 week
Other outcomes:
Locations:
city: Shiraz
country: Iran, Islamic Republic of
facility: Nemazi hospital
state: Fars
city: Shiraz
country: Iran, Islamic Republic of
facility: Faghihi hospital
state: Fars
Study officials:
affiliation: Shiraz University of medical sciences, department of neurology
name: Afshin Borhani Haghighi, Associate professor
role: PRINCIPAL_INVESTIGATOR
affiliation: Shiraz University of Medical Sciences
name: Farnia Feiz, medical student
role: STUDY_CHAIR
affiliation: Shiraz University of Medical Sciences
name: Reyhane Sedghi, medical student
role: STUDY_CHAIR
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