ANZCTR - Registration

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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 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]

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

Condition category

Condition code

Reproductive Health and Childbirth

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]

Treatment: Drugs

Comparator / control treatment

placebo tablet (microcellulose)

Control group

Placebo

Outcomes

Primary outcome [1]

Implantation rate

Timepoint [1]

pregnancy blood test (hCG) performed 2 weeks post embryo transfer

Primary outcome [2]

Clinical pregnancy rate

Timepoint [2]

assessed by ultrasound (fetal heart at 6 weeks post embryo transfer)

Secondary outcome [1]

Adverse events

Timepoint [1]

side effects of nifedipine (e.g. nausea, dizziness) as assessed by the patient 30 minutes post embryo transfer

Secondary outcome [2]

miscarriage (determined by ultrasound and blood test)

Timepoint [2]

pregnancy loss before 20 weeks gestation

Secondary outcome [3]

pregnancy outcomes (live birth or still birth as documented in medical records)

Timepoint [3]

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

Recruitment in Australia

Recruitment state(s)

VIC

Recruitment postcode(s) [1]

3002 - East Melbourne

Funding & Sponsors

Funding source category [1]

Other

Name [1]

Melbourne IVF

Address [1]

Melbourne IVF
344 Victoria Parade
East Melbourne VIC 3002

Country [1]

Australia

Primary sponsor type

Other

Name

Melbourne IVF

Address

344 Victoria Parade
East Melbourne, VIC, 3002

Country

Australia

Secondary sponsor category [1]

None

Name [1]

none

Address [1]

none

Country [1]

Ethics approval

Ethics application status

Approved

Ethics committee name [1]

Melbourne IVF HREC

Ethics committee address [1]

344 Victoria Parade
East Melbourne, VIC, 3002

Ethics committee country [1]

Australia

Date submitted for ethics approval [1]

13/10/2014

Approval date [1]

24/02/2015

Ethics approval number [1]

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

Dr Alex Polyakov

Address

Melbourne IVF
Suite 4, 320 Victoria Parade
East Melbourne, VIC, 3002

Country

Australia

Phone

+61 3 9486 0677

Fax

+61 3 9486 9161

[email protected]

Contact person for public queries

Name

Alex Polyakov

Address

Melbourne IVF
Suite 4, 320 Victoria Parade
East Melbourne, VIC, 3002

Country

Australia

Phone

+61 3 9486 0677

Fax

+61 3 9486 9161

[email protected]

Contact person for scientific queries

Name

Alex Polyakov

Address

Melbourne IVF
Suite 4, 320 Victoria Parade
East Melbourne, VIC, 3002

Country

Australia

Phone

+61 3 9486 0677

Fax

+61 3 9486 9161

[email protected]

Data sharing statement

Will individual participant data (IPD) for this trial be available (including data dictionaries)?

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.	Type	Citation	Link	Email	Other Details	Attachment
2320	Study protocol				https://journals.lww.com/md-journal/Fulltext/2017/... [More Details]

Results publications and other study-related documents

Documents added manually

No documents have been uploaded by study researchers.

Documents added automatically

No additional documents have been identified.

Trial Review

Documents added manually

Documents added automatically