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

NCT02159287 | Unknown Phase 2 DMC

• 1 other identifier: 92-01-01-5667
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 2

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.

Conditions

Embolic Stroke

Keywords

ischemic stroke; atrial fibrillation; bridging therapy

Outcome Measures

Primary Outcomes (3)

• mortality

  all death cases are included but only mortality due to cerebrovascular accident are considered.

  up to the 3 months of follow-up

• ischemic stroke

  Ischemic strokes are those that are caused by interruption of the blood supply

  up to the 3 months of follow-up

• hemorrhagic stroke

  hemorrhagic strokes are the ones which result from rupture of a blood vessel or an abnormal vascular structure.

  up to the 3 months of follow-up

Secondary Outcomes (5)

• symptomatic CNS hemorrhage

  up to the 3 months of follow-up

• Non-CNS hemorrhage

  up to the 3 months of follow-up

• asymptomatic CNS_hemorrhage

  up to the 3 months of follow-up

• time to reach target INR

  average time 7 to 10 days (it is variable between individuals)

• tolerability of drugs

  participants will be followed for the duration of hospital stay, an expected average of 1 week

Study Arms (2)

Low molecular-weight heparin

EXPERIMENTAL

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

unfractionated heparin

ACTIVE COMPARATOR

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

Interventions

Enoxaparin DRUG

1 mg of enoxaparin per kilogram of body weight subcutaneous every 12 hour

Also known as: clexane (Clexane, Sanofi, Paris)

Low molecular-weight heparin

Heparin DRUG

1000 unit per hour continuous intravenous infusion of heparin sodium

Also known as: Heparin Sodium (Alborz Darou,Tehran)

unfractionated heparin

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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

Sponsors & Collaborators

• Shiraz University of Medical Sciences: lead

Study Sites (2)

Nemazi hospital

Shiraz, Fars, 11351-71937, Iran

RECRUITING

Faghihi hospital

Shiraz, Fars, 7134844119, Iran

RECRUITING

Related Publications (11)

• Shahpouri MM, Mousavi S, Khorvash F, Mousavi SM, Hoseini T. Anticoagulant therapy for ischemic stroke: A review of literature. J Res Med Sci. 2012 Apr;17(4):396-401.

  PMID: 23267405 BACKGROUND

• Kase CS, Albers GW, Bladin C, Fieschi C, Gabbai AA, O'Riordan W, Pineo GF; PREVAIL Investigators. Neurological outcomes in patients with ischemic stroke receiving enoxaparin or heparin for venous thromboembolism prophylaxis: subanalysis of the Prevention of VTE after Acute Ischemic Stroke with LMWH (PREVAIL) study. Stroke. 2009 Nov;40(11):3532-40. doi: 10.1161/STROKEAHA.109.555003. Epub 2009 Aug 20.

  PMID: 19696423 BACKGROUND

• Algra A, de Schryver EL, van Gijn J, Kappelle LJ, Koudstaal PJ. Oral anticoagulants versus antiplatelet therapy for preventing further vascular events after transient ischaemic attack or minor stroke of presumed arterial origin. Cochrane Database Syst Rev. 2001;(4):CD001342. doi: 10.1002/14651858.CD001342.

  PMID: 11687110 BACKGROUND

• Saxena R, Lewis S, Berge E, Sandercock PA, Koudstaal PJ. Risk of early death and recurrent stroke and effect of heparin in 3169 patients with acute ischemic stroke and atrial fibrillation in the International Stroke Trial. Stroke. 2001 Oct;32(10):2333-7. doi: 10.1161/hs1001.097093.

  PMID: 11588322 BACKGROUND

• Hallevi H, Albright KC, Martin-Schild S, Barreto AD, Savitz SI, Escobar MA, Gonzales NR, Noser EA, Illoh K, Grotta JC. Anticoagulation after cardioembolic stroke: to bridge or not to bridge? Arch Neurol. 2008 Sep;65(9):1169-73. doi: 10.1001/archneur.65.9.noc70105. Epub 2008 Jul 14.

  PMID: 18625852 BACKGROUND

• Guyatt GH, Akl EA, Crowther M, Gutterman DD, Schuunemann HJ; American College of Chest Physicians Antithrombotic Therapy and Prevention of Thrombosis Panel. Executive summary: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012 Feb;141(2 Suppl):7S-47S. doi: 10.1378/chest.1412S3. No abstract available.

  PMID: 22315257 BACKGROUND

• Fahimi F, Baniasadi S, Behzadnia N. Enoxaparin Utilization Evaluation: An Observational Prospective Study in Medical Inpatients. Iranian Journal of Pharmaceutical Research 2008;7 (1):77-82.

  BACKGROUND

• Kalafut MA, Gandhi R, Kidwell CS, Saver JL. Safety and cost of low-molecular-weight heparin as bridging anticoagulant therapy in subacute cerebral ischemia. Stroke. 2000 Nov;31(11):2563-8. doi: 10.1161/01.str.31.11.2563.

  PMID: 11062276 BACKGROUND

• 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. doi: 10.1161/STROKEAHA.107.181486. Epub 2007 Apr 12.

  PMID: 17431204 BACKGROUND

• Cohen M, Demers C, Gurfinkel EP, Turpie AG, Fromell GJ, Goodman S, Langer A, Califf RM, Fox KA, Premmereur J, Bigonzi F. A comparison of low-molecular-weight heparin with unfractionated heparin for unstable coronary artery disease. Efficacy and Safety of Subcutaneous Enoxaparin in Non-Q-Wave Coronary Events Study Group. N Engl J Med. 1997 Aug 14;337(7):447-52. doi: 10.1056/NEJM199708143370702.

  PMID: 9250846 BACKGROUND

• Burak CR, Bowen MD, Barron TF. The use of enoxaparin in children with acute, nonhemorrhagic ischemic stroke. Pediatr Neurol. 2003 Oct;29(4):295-8. doi: 10.1016/s0887-8994(03)00270-4.

  PMID: 14643390 BACKGROUND

MeSH Terms

Conditions

Embolic Stroke; Ischemic Stroke; Atrial Fibrillation

Interventions

Enoxaparin; Heparin

Condition Hierarchy (Ancestors)

Stroke; Cerebrovascular Disorders; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Vascular Diseases; Cardiovascular Diseases; Arrhythmias, Cardiac; Heart Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Heparin, Low-Molecular-Weight; Glycosaminoglycans; Polysaccharides; Carbohydrates

Study Officials

• Afshin Borhani Haghighi, Associate professor

  Shiraz University of medical sciences, department of neurology

  PRINCIPAL INVESTIGATOR

• Farnia Feiz, medical student

  Shiraz University of Medical Sciences

  STUDY CHAIR

• Reyhane Sedghi, medical student

  Shiraz University of Medical Sciences

  STUDY CHAIR

Central Study Contacts

Afshin Borhani-Haghighi, Associate professor

CONTACT

00989177029134; Aborhani@sums.ac.ir

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Neurology Shiraz University of Medical Sciences

Study Record Dates

• First Submitted: January 20, 2014
• First Posted: June 9, 2014
• Study Start: January 1, 2014
• Primary Completion: February 1, 2016
• Study Completion: September 1, 2016
• Last Updated: June 9, 2014

Record last verified: 2014-06

Locations

IR (2)