Benefit of Amlodipine in HRT Cycle for Frozen Embryo Transfer in the Correction of Uterine Pulsatility Index

NCT04954196 | Withdrawn Phase 2 DMC

• 1 other identifier: RECHMPL20_0092
• Study Type: interventional
• Target: N/A
• Locations: 0 countries
• Sites: N/A

Brief Summary

Embryo implantation depends on two main factors: embryo grading quality and endometrial receptivity.Numerous tools have been suggested to evaluate these two factors. Measurement of the pulsatility index (PI) of the uterine arteries is associated with extremely low chances of pregnancy when it is high, especially higher than 3. A pilot study of women with premature ovarian failure with at least one of the uterine PIs greater than 3 showed the efficiency of nifedipine in uterine vascularization. This calcium channel blocker, used sublingually in this study, significantly lowered uterine PI in nearly half an hour. We are therefore interested in exploring this accessible, non-invasive and inexpensive tool, in the evaluation of endometrial receptivity before an embryo transfer.

Conditions

Frozen Embryo Transfer

Keywords

Frozen embryo transfer; Uterine artery pulsatility index; Implantation; Calcium channel blocker

Outcome Measures

Primary Outcomes (1)

• Number of patients with 2 PI less then 3 Vs number of patients who performed ultrasound

  Compare the rate of patients with two PIs on Dm + 7 (corresponding to D20-23 of the cycle) less than 3 out of the number of patients who performed the Doppler ultrasound in both arms.

  seven days after initiation of treatment: Dm+7

Secondary Outcomes (3)

• Number of clinical pregnancies VS number of embryo transfers

  6 to 8 weeks after embryo transfer

• number of miscarriages Vs number of embryo transfers

  before 20 weeks of menorrhea

• Number of live births Vs number of embryo transfers

  Delivery time starting 20 weeks of amenorrhea

Study Arms (2)

Amlodipine arm

EXPERIMENTAL

Single dose per os Amlodipine 5mg administration per day

Drug: Amlodipine 5mg

Placebo arm

PLACEBO COMPARATOR

Single dose per os placebo (microcrystalline cellulose) administration per day

Drug: Placebo

Interventions

Amlodipine 5mg DRUG

HRT administration: On Day 1 of the cycle, HRT is planned in accordance with the department's standard practice. * The frozen embryo transfer will be performed 6 days after progesterone initiation. * The HRT will be maintained until the pregnancy test is performed: If the test is positive,HRT will be continued for up to 12 weeks of amenorrhea at the same doses and then gradually stopped. If the test is negative,HRT will be stopped gradually Amlodipine administration: On the day of the first monitoring Dm (corresponding to D13 D16 of the cycle), a single per os dose of amlodipine 5 mg is taken at night, neither the patient nor the investigator knows what drug is the patient getting. Monitoring is systematically performed the next morning.The treatment will be maintained until the pregnancy test is performed then if the test is positive, the treatment will be maintained for a total duration of 7 weeks.

Also known as: AMLODIPINE ARROW GÉNÉRIQUES 5 mg

Amlodipine arm

Placebo DRUG

HRT administration: On Day 1 of the cycle, HRT is planned in accordance with the department's standard practice. * The frozen embryo transfer will be performed 6 days after progesterone initiation. * The HRT will be maintained until the pregnancy test is performed: If the test is positive, HRT will be continued for up to 12 weeks of amenorrhea at the same doses and then gradually stopped. If the test is negative, HRT will be stopped gradually Placebo administration:On the day of the first monitoring Dm (corresponding to D13-D16 of the cycle), a single per os dose of placebo (Microcrystalline cellulose) is taken at night, neither the patient nor the investigator knows what drug is the patient getting. Monitoring is systematically performed the next morning.. The treatment will be maintained until the pregnancy test is performed, then if the test is positive, the treatment will be maintained for a total duration of 7 weeks.

Placebo arm

Eligibility Criteria

• Age: 18 Years - 38 Years
• Gender Eligibility Details: Female patient scheduled for a blastocyst frozen transfer on HRT cycle
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Female subject
• years (≤) age (≤) 38 years
• Patient scheduled for a blastocyst frozen transfer (vitrification on Day 5) on HRT cycle (hormone replacement therapy)
• Measurement of at least one of the two uterine PI (pulsatility index) greater than 3 (\> 3) at the first monitoring Dm (corresponding to Day 13-Day 16 of the cycle)
• BMI ≤ 30 kg / m2
• Carrying out a transfer test qualified as easy (passage through the cervix of a flexible or rigid catheter, without anesthesia or Pozzi forceps)
• Collection and signature of free and informed consent
• Subject affiliated to or beneficiary of a health insurance plan

You may not qualify if:

• Active smoker patient (at least one cigarette a day at the enrollment in the study)
• Oocyte recipient patient
• A pre-implantation genetic screening (PGS) is planned for the patient
• Patient with stage 3 or 4 endometriosis, or adenomyosis
• Contraindication to the use of amlodipine (recent myocardial infarction less than one month old, severe angina pectoris, severe hepatic insufficiency, treatment with ciclosporin, hypotension, hypersensitivity to amlodipine, dihydropyridine derivatives)
• Concomitant use of inhibitors or enzyme inducers of CYP3A4
• Patient already being treated for high blood pressure
• Patient with an ovarian follicle recruitmant (\> 12mm) during the first monitoring (the most conservative case)
• Patient participating in another human intervention study
• Patient has already participated in this study
• Patient under legal protection, guardianship or curatorship
• Impossibility to give the patient clarifying information
• Impossibility to perform monitoring by an experienced sonographer
• Breastfeeding patient according to article L1121-5 of the CSP
• Patient protected or unable to give consent according to article L1121-8 of the Public Health Code (CSP)

Sponsors & Collaborators

• University Hospital, Montpellier: lead

MeSH Terms

Interventions

Amlodipine

Intervention Hierarchy (Ancestors)

Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds

Study Officials

• Noémie RANISAVLJEVIC, MD

  Arnaud de Villeneuve University Hospital, Montpellier

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Masking Details: Amlodipine 5 mg capsules (Arrow Generics®) will be deblistered and repackaged in pill boxes of 28 capsules. Placebo capsules will be made of microcrystalline cellulose and will be identical in size and color to generic Amlodipine Arrow capsules. A mass uniformity check will be carried out. Placebo capsules will also be packaged in pill boxes of 28 capsules.
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: July 5, 2021
• First Posted: July 8, 2021
• Study Start: October 8, 2021
• Primary Completion: October 8, 2023
• Study Completion: September 8, 2024
• Last Updated: March 13, 2023

Record last verified: 2023-03