Study of the Efficacy, Safety and Tolerability of Low Molecular Weight Heparin vs. Unfractionated Heparin in Stroke
|ClinicalTrials.gov Identifier: NCT02159287|
Recruitment Status : Unknown
Verified June 2014 by Afshin Borhani-Haghighi, Shiraz University of Medical Sciences.
Recruitment status was: Recruiting
First Posted : June 9, 2014
Last Update Posted : June 9, 2014
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.
|Condition or disease||Intervention/treatment||Phase|
|Embolic Stroke||Drug: Enoxaparin Drug: Heparin||Phase 2|
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||80 participants|
|Intervention Model:||Parallel Assignment|
|Masking:||Single (Outcomes Assessor)|
|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 Start Date :||January 2014|
|Estimated Primary Completion Date :||February 2016|
|Estimated Study Completion Date :||September 2016|
Experimental: Low molecular-weight heparin
these patients will receive 1 mg of enoxaparin (clexane) per kilogram of body weight subcutaneous every 12 hour with warfarin 5mg QD and both drugs will be continued until the target INR level (2.5) is reached then clexane will be discontinued.
1 mg of enoxaparin per kilogram of body weight subcutaneous every 12 hour
Other Name: clexane (Clexane, Sanofi, Paris)
Active Comparator: unfractionated heparin
This group will receive continuous intravenous unfractionated heparin sodium infusion 1000 unit per hour initially and then the dose will be adjusted to maintain a therapeutic aPTT level (two times to baseline) then warfarin will be started (5 mg QD).
1000 unit per hour continuous intravenous infusion of heparin sodium
Other Name: Heparin Sodium (Alborz Darou,Tehran)
- mortality [ Time Frame: up to the 3 months of follow-up ]all death cases are included but only mortality due to cerebrovascular accident are considered.
- ischemic stroke [ Time Frame: up to the 3 months of follow-up ]Ischemic strokes are those that are caused by interruption of the blood supply
- hemorrhagic stroke [ Time Frame: up to the 3 months of follow-up ]hemorrhagic strokes are the ones which result from rupture of a blood vessel or an abnormal vascular structure.
- symptomatic CNS hemorrhage [ Time Frame: up to the 3 months of follow-up ]Intracranial bleeding occurs when a blood vessel within the skull is ruptured or leaks that causes neurological symptoms. It can result from nontraumatic causes as occurs in hemorrhagic stroke such as a ruptured aneurysm. Anticoagulant therapy can heighten the risk that an intracranial hemorrhage will occur.
- Non-CNS hemorrhage [ Time Frame: up to the 3 months of follow-up ]any bleeding of other sites of body except CNS.
- asymptomatic CNS_hemorrhage [ Time Frame: up to the 3 months of follow-up ]Intracranial bleeding occurs when a blood vessel within the skull is ruptured or leaks that will not cause neurological symptoms. It can result from nontraumatic causes as occurs in hemorrhagic stroke such as a ruptured aneurysm. Anticoagulant therapy can heighten the risk that an intracranial hemorrhage will occur.
- time to reach target INR [ Time Frame: average time 7 to 10 days (it is variable between individuals) ]the therapeutic INR level for patients on warfarin therapy is between 2.0 to 3.0.
- tolerability of drugs [ Time Frame: participants will be followed for the duration of hospital stay, an expected average of 1 week ]tolerability is how a patient can tolerate heparin and LMWH in terms of side effect and route of administration.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02159287
|Contact: Afshin Borhani-Haghighi, Associate professor||00989177029134||Aborhani@sums.ac.ir|
|Iran, Islamic Republic of|
|Shiraz, Fars, Iran, Islamic Republic of, 11351-71937|
|Contact: Reyhane Sedghi, MD 00989177035783 email@example.com|
|Shiraz, Fars, Iran, Islamic Republic of, 7134844119|
|Contact: Farnia Feiz, MD 00989177383403 firstname.lastname@example.org|
|Principal Investigator:||Afshin Borhani Haghighi, Associate professor||Shiraz University of medical sciences, department of neurology|
|Study Chair:||Farnia Feiz, medical student||Shiraz University of Medical Sciences|
|Study Chair:||Reyhane Sedghi, medical student||Shiraz University of Medical Sciences|