Study of the Efficacy, Safety and Tolerability of Low Molecular Weight Heparin vs. Unfractionated Heparin in Stroke

This study is currently recruiting participants. (see Contacts and Locations)
Verified June 2014 by Shiraz University of Medical Sciences
Sponsor:
Information provided by (Responsible Party):
Afshin Borhani-Haghighi, Shiraz University of Medical Sciences
ClinicalTrials.gov Identifier:
NCT02159287
First received: January 20, 2014
Last updated: June 6, 2014
Last verified: June 2014
  Purpose

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 Intervention Phase
Embolic Stroke
Drug: Enoxaparin
Drug: Heparin
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Single Blind (Outcomes Assessor)
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Shiraz University of Medical Sciences:

Primary Outcome Measures:
  • mortality [ Time Frame: up to the 3 months of follow-up ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    hemorrhagic strokes are the ones which result from rupture of a blood vessel or an abnormal vascular structure.


Secondary Outcome Measures:
  • symptomatic CNS hemorrhage [ Time Frame: up to the 3 months of follow-up ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    any bleeding of other sites of body except CNS.

  • asymptomatic CNS_hemorrhage [ Time Frame: up to the 3 months of follow-up ] [ Designated as safety issue: Yes ]
    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) ] [ Designated as safety issue: Yes ]
    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 ] [ Designated as safety issue: Yes ]
    tolerability is how a patient can tolerate heparin and LMWH in terms of side effect and route of administration.


Estimated Enrollment: 80
Study Start Date: January 2014
Estimated Study Completion Date: September 2016
Estimated Primary Completion Date: February 2016 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
Drug: Enoxaparin
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).
Drug: Heparin
1000 unit per hour continuous intravenous infusion of heparin sodium
Other Name: Heparin Sodium (Alborz Darou,Tehran)

  Eligibility

Ages Eligible for Study:   18 Years to 75 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   Yes
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT02159287

Contacts
Contact: Afshin Borhani-Haghighi, Associate professor 00989177029134 Aborhani@sums.ac.ir

Locations
Iran, Islamic Republic of
Faghihi hospital Recruiting
Shiraz, Fars, Iran, Islamic Republic of, 7134844119
Contact: Farnia Feiz, MD    00989177383403    farniafeiz@gmail.com   
Nemazi hospital Recruiting
Shiraz, Fars, Iran, Islamic Republic of, 11351-71937
Contact: Reyhane Sedghi, MD    00989177035783    reihaneh.sedghi@gmail.com   
Sponsors and Collaborators
Shiraz University of Medical Sciences
Investigators
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
  More Information

Publications:
Adams HP Jr, del Zoppo G, Alberts MJ, Bhatt DL, Brass L, Furlan A, Grubb RL, Higashida RT, Jauch EC, Kidwell C, Lyden PD, Morgenstern LB, Qureshi AI, Rosenwasser RH, Scott PA, Wijdicks EF; American Heart Association; American Stroke Association Stroke Council; Clinical Cardiology Council; Cardiovascular Radiology and Intervention Council; Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups. Guidelines for the early management of adults with ischemic stroke: a guideline from the American Heart Association/American Stroke Association Stroke Council, Clinical Cardiology Council, Cardiovascular Radiology and Intervention Council, and the Atherosclerotic Peripheral Vascular Disease and Quality of Care Outcomes in Research Interdisciplinary Working Groups: the American Academy of Neurology affirms the value of this guideline as an educational tool for neurologists. Stroke. 2007 May;38(5):1655-711. Epub 2007 Apr 12. Erratum in: Stroke. 2007 Jun;38(6):e38. Stroke. 2007 Sep;38(9):e96.

Responsible Party: Afshin Borhani-Haghighi, Associate Professor of Neurology Shiraz University of Medical Sciences, Shiraz University of Medical Sciences
ClinicalTrials.gov Identifier: NCT02159287     History of Changes
Other Study ID Numbers: 92-01-01-5667
Study First Received: January 20, 2014
Last Updated: June 6, 2014
Health Authority: Iran: Ministry of Health

Keywords provided by Shiraz University of Medical Sciences:
ischemic stroke
atrial fibrillation
bridging therapy

Additional relevant MeSH terms:
Atrial Fibrillation
Cerebral Infarction
Stroke
Arrhythmias, Cardiac
Brain Diseases
Brain Infarction
Brain Ischemia
Cardiovascular Diseases
Central Nervous System Diseases
Cerebrovascular Disorders
Heart Diseases
Nervous System Diseases
Pathologic Processes
Vascular Diseases
Calcium heparin
Dalteparin
Heparin
Heparin, Low-Molecular-Weight
Anticoagulants
Cardiovascular Agents
Fibrin Modulating Agents
Fibrinolytic Agents
Hematologic Agents
Molecular Mechanisms of Pharmacological Action
Pharmacologic Actions
Therapeutic Uses

ClinicalTrials.gov processed this record on October 20, 2014