Efficacy and Safety of Crinone Versus Combination Medication (ACCESS)

Comparison of Crinone ® Versus Combination Medication for Luteal Phase Support on the Ongoing Pregnancy Rate of Frozen-thawed Cycle in Chinese Population a Randomized, Interventional, Open-label, Phase IV, Single Center, Pilot Study (ACCESS)

The study to compare to the efficacy and safety of Crinone versus combination medication in infertile women receive frozen-thawed embryo transfer (FET) in artificial cycles (AC).

Study Overview

• Status: Terminated
• Conditions: Infertility
• Intervention / Treatment: Drug: Crinone; Drug: Duphaston

• Study Type: Interventional
• Enrollment (Actual): 172
• Phase: Phase 4

Contacts and Locations

Study Locations

• China
  • Beijing, China, 100191
    • Peking University Third Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 38 years (Adult)
• Accepts Healthy Volunteers: No

Description

Inclusion Criteria:

Participants are eligible to be included in the study only if all the following criteria apply:

• Participants who will receive artificial frozen-thawed embryo transfer (FET) cycle study interventions
• Participants who have no more than two Day 5 embryos are planned to be transferred (follow the clinical practice of the study site)
• Participants have received estradiol valerate for no more than 20 days
• Participants have a transitional-endometrium of greater than or equal to 8 millimeter
• Participants have normal uterine cavity
• Participants can give signed informed consent
• Participants are willing to follow the study protocol and able to complete the study

Exclusion Criteria:

• Participants are willing to follow the study protocol and able to complete the study
• Participants with greater than or equal to three previously failed cycles of ET
• Participants with diseases that cannot tolerate pregnancy
• Hydrosalpinx
• Severe endometriosis (Endometriosis American Society for Reproductive Medicine (ASRM) criteria from 1996)
• Known hypersensitivity to progesterone, the excipients of Crinone and Duphaston Vaginal bleeding of unknown origin
• History of recurrent miscarriages
• Vaginitis
• Thromboembolic diseases (thrombophlebitis, thromboembolic disorder, or cerebral apoplexy) or participants with a history of these conditions
• Known or suspected progestogen-dependent neoplasm
• Participation in another clinical trial within the past 30 days
• Contraindications of both Crinone and Duphaston

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Crinone; Participants received Crinone 8% (90 milligrams [mg] an intravaginal progesterone gel contained in a single use, one piece applicator) once daily in morning from the day of endometrial transformation (Day -5) until ongoing pregnancy was confirmed up to Day 63.	Drug: Crinone; Participants received Crinone 8% (90 milligrams [mg] an intravaginal progesterone gel contained in a single use, one piece applicator) once daily in morning from the day of endometrial transformation (Day -5) until ongoing pregnancy was confirmed up to Day 63.
Experimental: Crinone plus Duphaston; Participants received Crinone 8% (90 mg an intravaginal progesterone gel contained in a single use, one piece applicator) once daily in morning followed by 10 mg of Duphaston tablet orally twice a day from the day of endometrial transformation (Day -5) until ongoing pregnancy was confirmed up to Day 63.	Drug: Crinone; Participants received Crinone 8% (90 milligrams [mg] an intravaginal progesterone gel contained in a single use, one piece applicator) once daily in morning from the day of endometrial transformation (Day -5) until ongoing pregnancy was confirmed up to Day 63.; Drug: Duphaston; Participants received 10 mg of Duphaston tablet orally twice a day from the day of endometrial transformation (Day -5) until ongoign pregnancy was confirmed up to Day 63.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ongoing Pregnancy Rate	Ongoing pregnancy was assessed by the presence of viable intra uterine fetus detected by ultrasound examination in 10-12 weeks of pregnancy (8 to 10 weeks after embryo transfer). Ongoing pregnancy rate is defined as the number of participants with ongoing pregnancy divided by the number of participants with embryo transfer (ET) multiplied by 100.	8 to 10 weeks after embryo transfer

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Beta Human Chorionic Gonadotrophin (Beta-hCG) Positive Rate	Beta-hCG positive rate defined as number of participants with positive beta-hCG divided by the number of participants with embryo transfer (ET) multiplied by 100.	2 weeks after embryo transfer
Implantation Rate	Implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred (ET) multiplied by 100.	4-6 weeks after embryo transfer
Clinical Pregnancy Rate	Clinical Pregnancy was defined as the pregnancy diagnosed by ultrasound of one or more gestational sacs or definitive clinical signs of pregnancy. Clinical pregnancy rate was measured as the number of participants with clinical pregnancy divided by number of participants with embryo transfer (ET) multiplied by 100.	4-6 weeks after embryo transfer
Early Abortion Rate	Early abortion defined as the spontaneous loss of an intra-uterine pregnancy prior to 12 completed weeks of gestational age. Early abortion rate defined as the number of participants with early abortion divided by number of participants with clinical pregnancy multiplied by 100.	Time from embryo transfer to 12 weeks of pregnancy
Luteal Phase Bleeding Rate	Luteal Phase Bleeding defined as the onset of any bleeding after embryo transfer and prior to the pregnancy test. Luteal phase bleeding rate defined as the number of participants with Luteal phase bleeding divided by number of participants with embryo transfer (ET) multiplied by 100.	2, 5 and 9 weeks after embryo transfer
Vaginal Bleeding Rate	Vaginal bleeding is defined as any bleeding recorded after a pregnancy test via serum Beta-Human Chorionic Gonadotrophin. Vaginal bleeding rate defined as the number of participants with vaginal bleeding divided by number of participants with embryo transfer (ET) multiplied by 100.	5 and 9 weeks after embryo transfer

Collaborators and Investigators

• Sponsor: Merck KGaA, Darmstadt, Germany
• Collaborators: Merck Serono Co., Ltd.
• Investigators: Study Director: Medical Responsible, Merck KGaA, Darmstadt, Germany

Publications and helpful links

Helpful Links

• Trial Awareness and Transparency website

Study record dates

Study Major Dates

• Study Start (Actual): May 31, 2019
• Primary Completion (Actual): October 27, 2021
• Study Completion (Actual): October 27, 2021

Study Registration Dates

• First Submitted: February 26, 2019
• First Submitted That Met QC Criteria: February 26, 2019
• First Posted (Actual): February 28, 2019

Study Record Updates

• Last Update Posted (Actual): March 12, 2024
• Last Update Submitted That Met QC Criteria: August 22, 2023
• Last Verified: August 1, 2023

More Information

Terms related to this study

• Keywords: Infertility; Frozen-thawed embryo transfer; Crinone; Duphaston; Chinese population
• Additional Relevant MeSH Terms: Urogenital Diseases; Genital Diseases; Infertility; Physiological Effects of Drugs; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Progestins; Dydrogesterone
• Other Study ID Numbers: MS200113_0005

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: We are committed to enhancing public health through responsible sharing of clinical trial data. Following approval of a new product or a new indication for an approved product in both the US and European Union, the study sponsor and/or its affiliated companies will share study protocols, anonymized patient data and study level data, and redacted clinical study reports with qualified scientific and medical researchers, upon request, as necessary for conducting legitimate research. Further information on how to request data can be found on our website bit.ly/IPD21
• IPD Sharing Time Frame: Within six months after the approval of a new product or a new indication for an approved product in both the United States and the European Union
• IPD Sharing Access Criteria: Qualified scientific and medical researchers can request the data. Such requests must be submitted in writing to the company's portal and will be internally reviewed regarding criteria for researchers' qualification and legitimacy of the research proposal.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No