The Study of the efficacy, safety and tolerability of low molecular weight heparin vs. unfractionated heparin in patients with embolic stroke due to atrial fibrillation
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 IV unfractionated heparin (UFH) until a standard aPTT is reached and then initiating warfarin. Another strategy is to use subcutaneous (SQ) injection of a low-molecular-weight heparin (LMWH) eg. Enoxaparin.
We 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 university affiliated teaching hospitals (Faghihi and Nemazi 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 QD 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 QD).
We 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 SPSS version 15 and Chi-square statistics. Main outcome of our study will be evaluation of new stroke, mortality, CNS hemorrhage, major bleeding, drop out and other unwanted side effects in first week and three months after stroke
General information
Acronym
IRCT registration information
IRCT registration number:IRCT2014020213698N1
Registration date:2014-02-02, 1392/11/13
Registration timing:registered_while_recruiting
Last update:
Update count:0
Registration date
2014-02-02, 1392/11/13
Registrant information
Name
Afshin Borhani Haghighi
Name of organization / entity
Shiraz University of Medical Sciences
Country
Iran (Islamic Republic of)
Phone
+98 71 1612 1065
Email address
aborhani@sums.ac.ir
Recruitment status
Recruitment complete
Funding source
Shiraz University of Medical Sciences
Expected recruitment start date
2014-01-01, 1392/10/11
Expected recruitment end date
2016-02-01, 1394/11/12
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
The Study of the efficacy, safety and tolerability of low molecular weight heparin vs. unfractionated heparin in patients with embolic stroke due to atrial fibrillation
Public title
The comparison of 2 types of heparin ( unfractionated vs low molecular weight heparin) in patients with stroke due to atrial fibrillation
Purpose
Prevention
Inclusion/Exclusion 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 MCA territory
NIHS score more than 20
hypersensitivity to IV UFH or LMWH
no informed consent
other causes for stroke except AF
pregnancy
breast feeding
uncontrolled HTN (BP more than 220/120)
renal, hepatic, respiratory or cardiac failure
myocardial infarction
infectious endocarditis
coma
vasculitis
dissection
Age
From 18 years old to 75 years old
Gender
Both
Phase
2
Groups that have been masked
No information
Sample size
Target sample size:
80
Randomization (investigator's opinion)
Randomized
Randomization description
Blinding (investigator's opinion)
Not blinded
Blinding description
Placebo
Not used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Vice chancellor for research affairs, ethics comittee
Street address
Zand Aenue
City
Shiraz
Postal code
Approval date
2013-12-25, 1392/10/04
Ethics committee reference number
92-01-01-5667
Health conditions studied
1
Description of health condition studied
ischemic stroke
ICD-10 code
I63.9
ICD-10 code description
A disorder characterized by a sudden loss of sensory function due to an intracranial vascular event. A group of pathological conditions characterized by sudden, non-convulsive loss of neurological function due to brain ischemia or intracranial hemorrhages
2
Description of health condition studied
persistent atrial fibrillation
ICD-10 code
I48
ICD-10 code description
Atrial fibrillation and flutter
3
Description of health condition studied
chronic atrial fibrillation
ICD-10 code
148.2
ICD-10 code description
Continuous or recurrent bouts of atrial fibrillation.
4
Description of health condition studied
paroxysmal atrial fibtillation
ICD-10 code
148.0
ICD-10 code description
Sudden and episodic bouts of atrial fibrillation.
Primary outcomes
1
Description
mortality
Timepoint
7 days and 90 days after stroke
Method of measurement
close observation in hospital and telephone interview after discharge
2
Description
ischemic stroke
Timepoint
7 days and 90 days after stroke
Method of measurement
CT scan and daily physical examination
3
Description
hemorrhagic stroke
Timepoint
7 days and 90 days after stroke
Method of measurement
CT scan and daily physical examination
Secondary outcomes
1
Description
symptomatic CNS hemorrhage
Timepoint
7 days and 90 days after stroke
Method of measurement
CT scan
2
Description
Non-CNS hemorrhage
Timepoint
7 days and 90 days after stroke
Method of measurement
CT scan
3
Description
asymptomatic CNS_hemorrhage
Timepoint
7 days and 90 days after stroke
Method of measurement
CT scan
4
Description
time to reach target INR
Timepoint
average time is 7 to 10 days (it is variable between individuals)
Method of measurement
laboratory
5
Description
tolerability of drugs
Timepoint
during hospital admission while the patient is receiving anticoagulant
Method of measurement
daily physical exam
Intervention groups
1
Description
Experimental: Low molecular-weight heparin( enoxaparin ; Clexane, Sanofi, Paris)
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.
Category
Treatment - Drugs
2
Description
Active Comparator: unfractionated heparin (alborz darou,Tehran)
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).
Category
Treatment - Drugs
Recruitment centers
1
Recruitment center
Name of recruitment center
Nemzi Hospital
Full name of responsible person
Farnia Feiz
Street address
Nemazi hospital, Nemazi Square, Shiraz
City
Shiraz
2
Recruitment center
Name of recruitment center
Shahid Fghighi Hospital
Full name of responsible person
Reihaneh Sedghi
Street address
Karim Khanezand blv, Shiraz
City
Shiraz
Sponsors / Funding sources
1
Sponsor
Name of organization / entity
Shiraz University of Medical Scienses
Full name of responsible person
Afshin Borhani-Haghighi
Street address
Vice Chancellor for research affaiars,Shiraz University of Medical Sciences, Zand Blv
City
Shiraz
Grant name
Grant code / Reference number
Is the source of funding the same sponsor organization/entity?
Yes
Title of funding source
Shiraz University of Medical Scienses
Proportion provided by this source
100
Public or private sector
empty
Domestic or foreign origin
empty
Category of foreign source of funding
empty
Country of origin
Type of organization providing the funding
empty
Person responsible for general inquiries
Contact
Name of organization / entity
Shiraz University of Medical Sciences
Full name of responsible person
Afshin Borhani-Haghighi
Position
Neurologist, Interventional neurology fellowship
Other areas of specialty/work
Street address
Zand Blv.
City
Shiraz
Postal code
Phone
+98 71 1612 1000
Fax
Email
borhanihaghighi@sums.ac.ir ,neuroab@gmail.com
Web page address
Person responsible for scientific inquiries
Contact
Name of organization / entity
Shiraz University of Medical Sciences
Full name of responsible person
Afshin Borhani-Hghighi
Position
Neurologist, Interventional neurology fellowship
Other areas of specialty/work
Street address
Motahari polyclinic, Nemazee sq.
City
Shiraz
Postal code
Phone
+98 71 1612 1000
Fax
Email
borhanihaghighi@sums.ac.ir ,neuroab@gmail.com
Web page address
Person responsible for updating data
Contact
Name of organization / entity
Shiraz University of Medical Sciences
Full name of responsible person
Afshin Borhani-Haghighi
Position
Neurologist, Interventional neurology fellowship
Other areas of specialty/work
Street address
Motahari Polyclinic, Nemazee Sq
City
Postal code
Phone
+98 71 1612 1000
Fax
Email
Web page address
Sharing plan
Deidentified Individual Participant Data Set (IPD)