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Trial registered on ANZCTR


Registration number
ACTRN12616001494426
Ethics application status
Approved
Date submitted
19/09/2016
Date registered
27/10/2016
Date last updated
27/10/2016
Type of registration
Retrospectively registered

Titles & IDs
Public title
Can treatment with nitric oxide donors improve pregnancy outcome in patients with history of unexplained recurrent early pregnancy loss?
Scientific title
Comparative study between placebo vaginal tablets and the nitric oxide donor isosorbide mononitrate 20 mg tablet applied vaginally for treatment of unexplained recurrent early pregnancy loss
Secondary ID [1] 290170 0
none
Universal Trial Number (UTN)
Trial acronym
Linked study record

Health condition
Health condition(s) or problem(s) studied:
fetal medicine 300445 0
complications of pregnancy 300446 0
unexplained recurrent early pregnancy loss 300447 0
unexplained recurrent early pregnancy loss 300448 0
Condition category
Condition code
Reproductive Health and Childbirth 300302 300302 0 0
Fetal medicine and complications of pregnancy

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
1-.A control group (120 cases) treated with placebo vaginal tablets once daily and a study group (105 cases) treated with isosorbide mononitrate 20 mg tablet applied vaginally once daily.
2-Treatment started from cycle day 21-23 to 12 weeks gestation if pregnancy occurs. If pregnancy does not occur participant repeat treatment next cycle at day 21-23.
3- Adherence to treatment was confirmed by empty drug packet return
4- A control group (120 cases) and a study group (105 cases).
Intervention code [1] 295928 0
Treatment: Drugs
Intervention code [2] 295929 0
Prevention
Comparator / control treatment
A control group (120 cases) with history of unexplained early recurrent pregnancy loss were treated with microcellulose tablet placebo vaginal tablets starting from cycle day 21-23 and continued till the end of the first trimester if pregnancy occurred
Control group
Placebo

Outcomes
Primary outcome [1] 299660 0
Take-home baby rate as assessed by review of medical records
Timepoint [1] 299660 0
End of pregnancy
Secondary outcome [1] 327765 0
Pregnancy loss rate assessed by review of medical records,
Timepoint [1] 327765 0
Twenty weeks gestation
Secondary outcome [2] 327766 0
Complications of pregnancy assessed by review of medical records
Timepoint [2] 327766 0
End of pregnancy
Secondary outcome [3] 327767 0
Uterine artery Doppler blood flow indices at cycle day 21-23 before treatment and at 12 weeks gestation
Timepoint [3] 327767 0
Twelve weeks gestation
Cycle day 21-23

Eligibility
Key inclusion criteria
The study included 225 patients with the following inclusion criteria: 1- Nulliparous aged 18-30 years, house-wives and nonsmokers. 2- History of two consecutive failed clinical pregnancies from the same husband during the first trimester and confirmed by ultrasound. 3- Normal levels of lupus anticoagulant and anticardiolipin IgG and IgM on two or more occasions at least 12 weeks apart. 4- Normal uterine cavity and no pelvic pathology diagnosed by 3D/4D ultrasound. Hysterography, Sono-hysterography, hysteroscopy and laparoscopy was done in few suspicious cases. 5- Normal blood glucose and hemoglobin A1c levels. 6- Normal serum TSH, serum prolactin and mid luteal phase serum progesterone levels >10 ng/ml. 7- Cytogenetic study of the parents was done for 14 patients who had the third loss during the study and feature no balanced reciprocal translocations.
Minimum age
18 Years
Maximum age
30 Years
Gender
Females
Can healthy volunteers participate?
No
Key exclusion criteria
Exclusion criteria include patients with cardiac disease, hypertension, sensitivity to NO donors and cases of interim ectopic or molar pregnancy or blighted ovum.

Study design
Purpose of the study
Treatment
Allocation to intervention
Randomised controlled trial
Procedure for enrolling a subject and allocating the treatment (allocation concealment procedures)
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
Masking / blinding
Who is / are masked / blinded?



Intervention assignment
Other design features
Phase
Type of endpoint(s)
Statistical methods / analysis

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] 8245 0
Egypt
State/province [1] 8245 0

Funding & Sponsors
Funding source category [1] 294537 0
Hospital
Name [1] 294537 0
Banha University Hospital
Address [1] 294537 0
Farid Nada st. Banha; Kalupia Goernorate; Egypt
Country [1] 294537 0
Egypt
Primary sponsor type
Hospital
Name
Banha University Hospital
Address
Farid Nada St. Banha; Kalupia
Country
Egypt
Secondary sponsor category [1] 293408 0
None
Name [1] 293408 0
Address [1] 293408 0
Country [1] 293408 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 295974 0
Ethics committee of the department of OB/GYN
Ethics committee address [1] 295974 0
Banha University Hospital. Banha; Farid Nada St.Kalupia governorate.
Ethics committee country [1] 295974 0
Egypt
Date submitted for ethics approval [1] 295974 0
01/12/2012
Approval date [1] 295974 0
01/12/2012
Ethics approval number [1] 295974 0
NA

Summary
Brief summary
Objectives: Impairment of endogenous nitric oxide synthesis is claimed a subtle cause of recurrent pregnancy loss. The present study evaluates treatment with the nitric oxide donor isosorbide mononitrate. Methods: Two hundred twenty five nulliparous with history of two consecutive unexplained pregnancy losses during the first trimester were randomized to a control group (120 cases) treated with placebo vaginal tablets and a study group (105) treated with isosorbide mononitrate 20 mg applied vaginally. Treatment started from day 21-23 of the cycle until menstruation and continued if pregnancy occurred until the end of the first trimester. Vaginal color Doppler ultrasound was done before treatment and at 12 weeks gestation to measure uterine artery resistance and pulsation indices. The outcomes of pregnancies in both groups were compared and statistically analyzed. Results: The study group had significant higher take-home baby rate, significant lower pregnancy loss and preeclampsia rates and lower mean uterine artery resistance and pulsation indices at 12 weeks gestation (p<0.05). Conclusions: Treatment of unexplained recurrent pregnancy loss patients with the nitric oxide donor isosorbide mononitrate is associated with better pregnancy outcomes.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 69098 0
Prof Mohamed Abdelrazik
Address 69098 0
Department of OB/GYN, Banha University Hospital,; Banha; Farid Nada St. Kalupia governorate,
Country 69098 0
Egypt
Phone 69098 0
+200226070837
Fax 69098 0
Email 69098 0
prof.mohamedabdelrazik@hotmail.com
Contact person for public queries
Name 69099 0
Prof Mohamed Abdelrazik
Address 69099 0
Department of OB/GYN, Banha University Hospital, Banha; Farid Nada St.; Kalupia governorate
Country 69099 0
Egypt
Phone 69099 0
+200226070837
Fax 69099 0
NA
Email 69099 0
prof.mohamedabdelrazik@hotmail.com
Contact person for scientific queries
Name 69100 0
Prof Mohamed Abdelrazik
Address 69100 0
Department of OB/GYN, Banha University Hospital; Banha; Farid Nada St. Kalupia governorate
Country 69100 0
Egypt
Phone 69100 0
+200226070837
Fax 69100 0
NA
Email 69100 0
prof.mohamedabdelrazik@hotmail.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