Trial Review

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Trial registered on ANZCTR


Registration number
ACTRN12617000213347
Ethics application status
Approved
Date submitted
12/12/2016
Date registered
9/02/2017
Date last updated
14/06/2019
Date data sharing statement initially provided
13/06/2019
Date results information initially provided
13/06/2019
Type of registration
Retrospectively registered

Titles & IDs
Public title
Does nifedipine improve implantation and pregnancy rates in women undergoing in-vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles?
Scientific title
Does nifedipine improve implantation and pregnancy rates in women undergoing in-vitro fertilisation (IVF)/intracytoplasmic sperm injection (ICSI) cycles?
Secondary ID [1] 290567 0
nil
Universal Trial Number (UTN)
Trial acronym
NIPA Trial (Nifedipine for improving Implantation and Pregnancy rates in ART)
Linked study record

Health condition
Health condition(s) or problem(s) studied:
infertility 301017 0
Condition category
Condition code
Reproductive Health and Childbirth 300812 300812 0 0
Fertility including in vitro fertilisation

Intervention/exposure
Study type
Interventional
Description of intervention(s) / exposure
Nifedipine (20mg oral tablet, immediate release preparation) administered once only 30 minutes prior to embryo transfer
Intervention code [1] 296435 0
Treatment: Drugs
Comparator / control treatment
placebo tablet (microcellulose)
Control group
Placebo

Outcomes
Primary outcome [1] 300234 0
Implantation rate

Timepoint [1] 300234 0
pregnancy blood test (hCG) performed 2 weeks post embryo transfer
Primary outcome [2] 300499 0
Clinical pregnancy rate
Timepoint [2] 300499 0
assessed by ultrasound (fetal heart at 6 weeks post embryo transfer)
Secondary outcome [1] 329440 0
Adverse events
Timepoint [1] 329440 0
side effects of nifedipine (e.g. nausea, dizziness) as assessed by the patient 30 minutes post embryo transfer
Secondary outcome [2] 330140 0
miscarriage (determined by ultrasound and blood test)
Timepoint [2] 330140 0
pregnancy loss before 20 weeks gestation
Secondary outcome [3] 330141 0
pregnancy outcomes (live birth or still birth as documented in medical records)
Timepoint [3] 330141 0
at birth

Eligibility
Key inclusion criteria
* 18-45yo females undergoing IVF/ICSI cycles with either fresh or frozen embryo transfer.
* Baseline Blood Pressure: greater than, or equal to, 100/60, measured prior to ET
Minimum age
18 Years
Maximum age
45 Years
Sex
Females
Can healthy volunteers participate?
Yes
Key exclusion criteria
*Body mass index (BMI) > 38 kg/m2
*Early follicular phase (day 2-4) serum follicle stimulating hormone (FSH) level > 20 mIU/ml.
*Abnormal uterine cavity as evidenced by sonohysterogram or hysterosalpingography
*Any contraindication to being pregnant and carrying a pregnancy to term.
* Contraindication for the use of nifedipine, Estrogen and Progesterone suppositories.
* Patient being treated with other drugs that interact with cytochrome P450 activity: azole antifungals, cimetidine, cyclosporine, erythromycin, quinidine, terfenadine, warfarin, benzodiazepines, flecainide, imipramine, propafenone and theophylline.*Irregular heart beat or already being treated with another medication for high blood pressure.
*Any ovarian or abdominal abnormality that may interfere with adequate transvaginal sonography (TVS) evaluation.
*Administration of any investigational drugs within three months prior to study enrollment.
*Patient not able to communicate adequately with the investigators and to comply with the requirements of the entire study.
*Unwillingness to give written informed consent.
*Previous entry into this study.
*BP <100/60

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)
sealed opaque envelopes
Methods used to generate the sequence in which subjects will be randomised (sequence generation)
computer generated block randomization
Masking / blinding
Blinded (masking used)
Who is / are masked / blinded?
The people receiving the treatment/s
The people administering the treatment/s
The people assessing the outcomes
The people analysing the results/data
Intervention assignment
Parallel
Other design features
none
Phase
Phase 1
Type of endpoint/s
Safety/efficacy
Statistical methods / analysis
Being a pilot proof of concept study there are no data that can be utilised to calculate sample size for this study. Investigators feel that relatively small sample size of 50 participants in each arm would be sufficient to demonstrate any serious adverse events that could inform future design of a larger study. This small sample may also be able to detect any large difference in outcomes such as pregnancy rates but the magnitude of effect would need to be quite substantial.
It is anticipated that Student’s t test will be used for continuous variables and Chi-square test to asses differences in proportions. Due to small sample size non-parametric equivalents of the above tests will also be used. It is anticipated that a regression analysis will be undertaken in order to control for important variables such as female age, BMI, etc.

Recruitment
Recruitment status
Completed
Date of first participant enrolment
Anticipated
Actual
6/09/2015
Date of last participant enrolment
Anticipated
24/04/2017
Actual
10/04/2017
Date of last data collection
Anticipated
30/04/2018
Actual
18/01/2018
Sample size
Target
100
Accrual to date
Final
93
Recruitment in Australia
Recruitment state(s)
VIC
Recruitment postcode(s) [1] 14646 0
3002 - East Melbourne

Funding & Sponsors
Funding source category [1] 295004 0
Other
Name [1] 295004 0
Melbourne IVF
Country [1] 295004 0
Australia
Primary sponsor type
Other
Name
Melbourne IVF
Address
344 Victoria Parade
East Melbourne, VIC, 3002
Country
Australia
Secondary sponsor category [1] 293822 0
None
Name [1] 293822 0
none
Address [1] 293822 0
none
Country [1] 293822 0

Ethics approval
Ethics application status
Approved
Ethics committee name [1] 296357 0
Melbourne IVF HREC
Ethics committee address [1] 296357 0
344 Victoria Parade
East Melbourne, VIC, 3002
Ethics committee country [1] 296357 0
Australia
Date submitted for ethics approval [1] 296357 0
13/10/2014
Approval date [1] 296357 0
24/02/2015
Ethics approval number [1] 296357 0
36/14-MIVF

Summary
Brief summary
Implantation failure is the main factor affecting the success rate of IVF procedures. Excessive uterine contractions have been described as a potential reason for reduced implantation rates in IVF cycles. Contractile activity of the uterus could move the implanted embryo towards the Fallopian tubes or cervix/vagina or the embryo might even be expelled out of the uterus.

Mechanical measures to reduce the uterine contractions at the time of embryo transfer include using a soft catheter without touching the fundus (the top of the uterus) and the use of ultrasound to guide embryo transfer. Various medications have been investigated to reduce uterine contractions, including cyclo-oxygenase inhibitors, B2-adrenoreceptor agonists, phosphodiesterase inhibitors. These have yielded variable results with atosiban, an oxytocin/vasopressin receptor antagonist, looking most promising for improving implantation and pregnancy rates.

Calcium channel blockers are non-specific smooth muscle relaxants, used for the treatment of high blood pressure in adults and have an established role in preterm labour due to its uterine relaxing properties. In the uterus, the calcium channel blockers exert their “anti-contraction” effect by preventing the influx of extracellular calcium ions into the myometrial cell (the middle wall of the uterus) and have been demonstrated in laboratory experiments to have potent relaxant effect on human myometrium (the middle wall of the uterus). The most widely used and studied calcium channel blocker is nifedipine and there is evidence that this can be safely used in pregnancy.

The objective of this study is to evaluate the effectiveness of nifedipine administration in improving implantation and pregnancy rates in IVF/ICSI fresh or frozen embryo transfers.
Trial website
Trial related presentations / publications
Public notes

Contacts
Principal investigator
Name 70574 0
Dr Alex Polyakov
Address 70574 0
Melbourne IVF
Suite 4, 320 Victoria Parade
East Melbourne, VIC, 3002
Country 70574 0
Australia
Phone 70574 0
+61 3 9486 0677
Fax 70574 0
+61 3 9486 9161
Email 70574 0
[email protected]
Contact person for public queries
Name 70575 0
Dr Alex Polyakov
Address 70575 0
Melbourne IVF
Suite 4, 320 Victoria Parade
East Melbourne, VIC, 3002
Country 70575 0
Australia
Phone 70575 0
+61 3 9486 0677
Fax 70575 0
+61 3 9486 9161
Email 70575 0
[email protected]
Contact person for scientific queries
Name 70576 0
Dr Alex Polyakov
Address 70576 0
Melbourne IVF
Suite 4, 320 Victoria Parade
East Melbourne, VIC, 3002
Country 70576 0
Australia
Phone 70576 0
+61 3 9486 0677
Fax 70576 0
+61 3 9486 9161
Email 70576 0
[email protected]

Data sharing statement
Will individual participant data (IPD) for this trial be available (including data dictionaries)?
No
No/undecided IPD sharing reason/comment
outcomes of the study did not necessitate individual participant data to be made available. All data will be presented in an article as an aggregate result and will be deidentified.


What supporting documents are/will be available?

Doc. No.TypeCitationLinkEmailOther DetailsAttachment
2320Study protocol    https://journals.lww.com/md-journal/Fulltext/2017/... [More Details]



Results publications and other study-related documents

Documents added manually

Documents added automatically
No additional documents have been identified.