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

NCT ID: NCT02159287

Last Updated: 2014-06-09

Study Results

Results pending

The study team has not published outcome measurements, participant flow, or safety data for this trial yet. Check back later for updates.

Basic Information

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Recruitment Status

UNKNOWN

Clinical Phase

PHASE2

Total Enrollment

80 participants

Study Classification

INTERVENTIONAL

Study Start Date

2014-01-31

Study Completion Date

2016-09-30

Brief Summary

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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.

Detailed Description

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Conditions

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Embolic Stroke

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

Primary Study Purpose

PREVENTION

Blinding Strategy

SINGLE

Outcome Assessors

Study Groups

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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.

Group Type EXPERIMENTAL

Enoxaparin

Intervention Type DRUG

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

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).

Group Type ACTIVE_COMPARATOR

Heparin

Intervention Type DRUG

1000 unit per hour continuous intravenous infusion of heparin sodium

Interventions

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Enoxaparin

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

Intervention Type DRUG

Heparin

1000 unit per hour continuous intravenous infusion of heparin sodium

Intervention Type DRUG

Other Intervention Names

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clexane (Clexane, Sanofi, Paris) Heparin Sodium (Alborz Darou,Tehran)

Eligibility Criteria

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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
Minimum Eligible Age

18 Years

Maximum Eligible Age

75 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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Shiraz University of Medical Sciences

OTHER

Sponsor Role lead

Responsible Party

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Afshin Borhani-Haghighi

Associate Professor of Neurology Shiraz University of Medical Sciences

Responsibility Role PRINCIPAL_INVESTIGATOR

Principal Investigators

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Afshin Borhani Haghighi, Associate professor

Role: PRINCIPAL_INVESTIGATOR

Shiraz University of medical sciences, department of neurology

Farnia Feiz, medical student

Role: STUDY_CHAIR

Shiraz University of Medical Sciences

Reyhane Sedghi, medical student

Role: STUDY_CHAIR

Shiraz University of Medical Sciences

Locations

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Nemazi hospital

Shiraz, Fars, Iran

Site Status RECRUITING

Faghihi hospital

Shiraz, Fars, Iran

Site Status RECRUITING

Countries

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Iran

Central Contacts

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Afshin Borhani-Haghighi, Associate professor

Role: CONTACT

00989177029134

Facility Contacts

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Reyhane Sedghi, MD

Role: primary

00989177035783

Farnia Feiz, MD

Role: primary

00989177383403

References

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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.

Reference Type BACKGROUND
PMID: 23267405 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 19696423 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11687110 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 11588322 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 18625852 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 22315257 (View on PubMed)

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.

Reference Type 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.

Reference Type BACKGROUND
PMID: 11062276 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 17431204 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 9250846 (View on PubMed)

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.

Reference Type BACKGROUND
PMID: 14643390 (View on PubMed)

Other Identifiers

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92-01-01-5667

Identifier Type: -

Identifier Source: org_study_id

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