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Trial registered on ANZCTR


Registration number
ACTRN12614000357651
Ethics application status
Approved
Date submitted
20/03/2014
Date registered
4/04/2014
Date last updated
4/04/2014
Type of registration
Retrospectively registered

Titles & IDs
Public title
Pregnancy outcome in women with mechanical prosthetic heart valves treated with Unfractionated Heparin (UFH) or enoxaparin
Scientific title
Pregnancy outcome in women with mechanical prosthetic heart valves treated with Unfractionated Heparin (UFH) or enoxaparin
Secondary ID [1] 284291 0
none
Universal Trial Number (UTN)
U1111-1154-6638
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
For pregnant women with mechanical heart valves 291436 0
Condition category
Condition code
Cardiovascular 291810 291810 0 0
Other cardiovascular diseases
Reproductive Health and Childbirth 291891 291891 0 0
Antenatal care

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Women were reviewed urgently upon confirmation of pregnancy (at booking) to discuss with them treatment options and the risks of continuing the pregnancy. Women were informed of both the maternal and fetal risks associated with anticoagulant regimen choices and fully participated in the decision process of anticoagulation.
After her choice of one of the following treatment options each pregnant woman completed written informed consent:

A). Replacement of warfarin with therapeutic dose UFH (15.000 IU/twice daily given subcutaneously) before 6 weeks’ gestation, continued throughout pregnancy but stopped 12 hours before delivery is anticipated and can be restarted, in the absence of hemorrhagic problems, 4 to 6 hours after delivery.

B). Replacement of warfarin with therapeutic dose enoxaparin (1 mg/kg twice daily given subcutaneously ) before 6 weeks’ gestation, continued until 36th week gestation then shift to UFH until delivery by 15.000 IU/twice daily given subcutaneously .In the intrapartum setting, heparin injection should be stopped 12 hours before delivery is anticipated and can be restarted, in the absence of hemorrhagic problems, 4 to 6 hours after delivery.

During (UFH) treatment group A, the activated partial thromboplastin time (aPTT) was maintained at twice the control level.
For women in enoxaparin group(B), monitoring of anti-Xa levels was recommended every month, our aim for target levels of Anti-Xa was 0.7 to 1.2 IU/ml /4 hours post dose . Anti-Xa levels were first checked 3–7 days after starting treatment or following dose modification and then repeated monthly at routine prenatal visits, adjusting the level upward or downward as necessary

Thus, we had two study groups according to the anticoagulation regimen. A total of 20 patients were on UFH throughout their pregnancy (group A). The remaining 20 patients (group B) had enoxaparin till the 36th week of gestation followed by heparin for the last two weeks of pregnancy; heparin stopped 12 hours before delivery is anticipated and can be restarted, in the absence of hemorrhagic problems, 4 to 6 hours after delivery.

Intervention code [1] 289014 0
Treatment: Drugs
Comparator / control treatment
Group A. (Replacement of warfarin with therapeutic dose UFH (15.000 IU/twice daily given subcutaneously) before 6 weeks’ gestation, continued until delivery.)
Control group
Active

Outcomes
Primary outcome [1] 291726 0
The primary outcome measure was the rate of live births
Timepoint [1] 291726 0
at time of delivery
Secondary outcome [1] 307358 0
Secondary outcomes included rates of miscarriage
Timepoint [1] 307358 0
throughout the duration of pregnancy
Secondary outcome [2] 307472 0
intrauterine fetal death (fetal death after 20 weeks of gestation),
Timepoint [2] 307472 0
throughout the pregnancy
Secondary outcome [3] 307473 0
obstetrical complications e.g small size for gestational age
Timepoint [3] 307473 0
during third trimester
Secondary outcome [4] 307474 0
maternal thrombotic complications and maternal death
Timepoint [4] 307474 0
throughtout pregnancy
Secondary outcome [5] 307475 0
postpartum hemorrage
Timepoint [5] 307475 0
after delivery

Eligibility
Key inclusion criteria
40 pregnant women with prosthetic heart valves were followed in the high-risk pregnancy unit- Benha university hospital and were interviewed about their medical, personal, family, obstetrical and thrombosis history.
Minimum age
21 Years
Maximum age
44 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
none

Study design
Purpose of the study
Treatment
Allocation to intervention
Non-randomised trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Women were reviewed urgently upon confirmation of pregnancy (at booking) to discuss with them treatment options and the risks of continuing the pregnancy. Women were informed of both the maternal and fetal risks associated with anticoagulant regimen choices and fully participated in the decision process of anticoagulation.
After her choice of one of the following treatment options each pregnant woman completed written informed consent:
A). Replacement of warfarin with therapeutic dose UFH (15.000 IU/12 hour) before 6 weeks’ gestation, continued througout pregnancy but stopped 12 hours before delivery.
B). Replacement of warfarin with therapeutic dose enoxaparin (1 mg/kg bid) before 6 weeks’ gestation, continued until 36th week gestation then shift to UFH until 12 hours before delivery.

Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Open (masking not used)
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Phase 1 / Phase 2
Type of endpoint(s)
Safety/efficacy
Statistical methods / analysis
Results were expressed as mean+/- SD, range, numbers and percentages. Intra-Group data was statistically analyzed using t-test and inter-Group analysis was examined using Chisquare test (X^2 test). Statistical analysis was conducted using SPSS statistical program, (Version 10, 2002). P value <0.05 was considered statistically significant.
sample size calculation was according to the following formula:

N = 2Standard deviation X K / E2


*Standard deviation: population of previous literature
*K : constant (7.8) from statistical table
*E2: minimal change in mean that would be clinical

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
Date of last participant enrolment
Anticipated
Actual
Date of last data collection
Anticipated
Actual
Sample size
Target
Accrual to date
Final
Recruitment outside Australia
Country [1] 5907 0
Egypt
State/province [1] 5907 0

Funding & Sponsors
Funding source category [1] 288922 0
Self funded/Unfunded
Name [1] 288922 0
Address [1] 288922 0
Country [1] 288922 0
Primary sponsor type
Individual
Name
khalid abd aziz mohamed
Address
Benha University, Faculty of Medicine
el saha street
Benha city
Qalubiya Governorate
Egypt
13518
Country
Egypt
Secondary sponsor category [1] 287614 0
Individual
Name [1] 287614 0
ahmed samy saad
Address [1] 287614 0
Benha University, Faculty of Medicine
el saha street
Benha city
Qalubiya Governorate
Egypt
13518
Country [1] 287614 0
Egypt

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 290750 0
Department of Obstetrics and Gynecology, Benha University Hospital Local Ethical Committee
Ethics committee address [1] 290750 0
Benha city
el saha street
Qalubiya Governorate
Egypt
13518
Ethics committee country [1] 290750 0
Egypt
Date submitted for ethics approval [1] 290750 0
Approval date [1] 290750 0
Ethics approval number [1] 290750 0

Summary
Brief summary
Objective :To determine maternal (included thromboembolic and haemorrhagic complications) and fetal outcomes(included miscarriage, stillbirth, baby death and live birth) in women with mechanical heart valves managed with therapeutic dose unfractionated Heparin (UFH) versus enoxaparin during pregnancy.
Methods: this is a prospective comparative, non-randomized study.Pregnant women with mechanical heart valves attending high-risk pregnancy unit high-Benha university hospital, treated with Unfractionated Heparin (UFH) 15,000 U /12 h versus enoxaparin (Clexane) 1mg/kg subcutaneously /12h during pregnancy.
Results: 40 pregnant. In 20 pregnancies anticoagulation was with Unfractionated Heparin (UFH) and 20 pregnancies women received enoxaparin. One (3%) thrombotic complications occurred with enoxaparin treatment. Non-compliance or sub-therapeutic levels contributed in this case. Antenatal hemorrage occurred in 4 (10%) and postpartum haemorrhagic complications in 5 (12.5%) pregnancies. Of 32 pregnancies continued after 20 weeks’ gestation, 100% (17/17) of women taking predominantly Unfractionated Heparin (UFH) had a surviving infant compared with 93% (14/15) in women taking primarily enoxaparin(p equal to 0.25). One intrauterine fetal death (IUFD) occurred in enoxaparin group. There was no significant difference in live birth rate between the two groups (p equal to 0.31).
Conclusions: Compliance with therapeutic dose Unfractionated Heparin (UFH) during pregnancy in women with mechanical heart valves is associated with a low risk of valve thrombosis and good fetal outcomes, but meticulous monitoring is essential.
Keywords: enoxaparin, prosthetic heart valves, UFH, pregnancy, thromboembolism.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 47062 0
Dr khalid abd aziz mohamed
Address 47062 0
Benha University, Faculty of Medicine
el saha street
Benha city
Qalubiya Governorate
13518
Country 47062 0
Egypt
Phone 47062 0
+2001281469651
Fax 47062 0
Email 47062 0
dr.khalidkhader77@yahoo.com
Contact person for public queries
Name 47063 0
Dr khalid abd aziz mohamed
Address 47063 0
Benha University, Faculty of Medicine
el saha street
Benha city
13518
Qalubiya Governorate
Country 47063 0
Egypt
Phone 47063 0
+2001281469651
Fax 47063 0
Email 47063 0
dr.khalidkhader77@yahoo.com
Contact person for scientific queries
Name 47064 0
Dr khalid abd aziz mohamed
Address 47064 0
Benha University, Faculty of Medicine
el saha street
13518
Benha city
Qalubiya Governorate
Country 47064 0
Egypt
Phone 47064 0
+2001281469651
Fax 47064 0
Email 47064 0
dr.khalidkhader77@yahoo.com

No information has been provided regarding IPD availability
Summary results
Have study results been published in a peer-reviewed journal?
Other publications
Have study results been made publicly available in another format?
Results – basic reporting
Results – plain English summary