Trial Outcomes & Findings for Efficacy and Safety of Crinone Versus Combination Medication (ACCESS) (NCT NCT03858049)

Results Overview

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.

Recruitment status

TERMINATED

Study phase

PHASE4

Target enrollment

172 participants

Primary outcome timeframe

8 to 10 weeks after embryo transfer

Results posted on

2024-03-12

Participant Flow

Participant milestones

Participant milestones
Measure	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.	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.
Overall Study STARTED	86	86
Overall Study COMPLETED	69	76
Overall Study NOT COMPLETED	17	10

Reasons for withdrawal

Reasons for withdrawal
Measure	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.	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.
Overall Study Adverse Event	16	9
Overall Study Other	1	1

Baseline Characteristics

Efficacy and Safety of Crinone Versus Combination Medication (ACCESS)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Crinone n=86 Participants 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.	Crinone® Plus Duphaston n=86 Participants 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.	Total n=172 Participants Total of all reporting groups
Age, Continuous	30.84 Years STANDARD_DEVIATION 2.918 • n=5 Participants	30.74 Years STANDARD_DEVIATION 3.163 • n=7 Participants	30.79 Years STANDARD_DEVIATION 3.034 • n=5 Participants
Sex: Female, Male Female	86 Participants n=5 Participants	86 Participants n=7 Participants	172 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	86 Participants n=5 Participants	86 Participants n=7 Participants	172 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) White	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants

PRIMARY outcome

Timeframe: 8 to 10 weeks after embryo transfer

Population: ITT Population included all participants who received at least one dose of randomized study intervention. Here, "Number of participants analyzed" signified those participants who had embryo transferred.

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.

Outcome measures

Outcome measures
Measure	Crinone n=85 Participants 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.	Crinone® Plus Duphaston n=86 Participants 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.
Ongoing Pregnancy Rate	18.8 Percentage of participants Interval 11.2 to 28.8	29.1 Percentage of participants Interval 19.8 to 39.9

SECONDARY outcome

Timeframe: 2 weeks after embryo transfer

Population: ITT Population included all participants who received at least one dose of randomized study intervention. Here, "Number of participants analyzed" signified those participants who had embryo transferred.

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.

Outcome measures

Outcome measures
Measure	Crinone n=85 Participants 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.	Crinone® Plus Duphaston n=86 Participants 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.
Beta Human Chorionic Gonadotrophin (Beta-hCG) Positive Rate	37.6 Percentage of participants Interval 27.4 to 48.8	43.0 Percentage of participants Interval 32.4 to 54.2

SECONDARY outcome

Timeframe: 4-6 weeks after embryo transfer

Population: ITT Population included all participants who received at least one dose of randomized study intervention.

Implantation rate was measured as the number of gestational sacs observed divided by the number of embryos transferred (ET) multiplied by 100.

Outcome measures

Outcome measures
Measure	Crinone n=86 embroys transferred 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.	Crinone® Plus Duphaston n=86 embroys transferred 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.
Implantation Rate	20.9 percentage of gestational sacs per ET Interval 12.9 to 31.0	33.7 percentage of gestational sacs per ET Interval 23.9 to 44.7

SECONDARY outcome

Timeframe: 4-6 weeks after embryo transfer

Population: ITT Population included all participants who received at least one dose of randomized study intervention. Here, "Number of participants analyzed" signified those participants who had embryo transferred.

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.

Outcome measures

Outcome measures
Measure	Crinone n=85 Participants 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.	Crinone® Plus Duphaston n=86 Participants 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.
Clinical Pregnancy Rate	21.2 Percentage of participants Interval 13.1 to 31.4	33.7 Percentage of participants Interval 23.9 to 44.7

SECONDARY outcome

Timeframe: Time from embryo transfer to 12 weeks of pregnancy

Population: ITT Population included all participants who received at least one dose of randomized study intervention. Here, "Number of participants analyzed" signified those participants with clinical pregnancy.

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.

Outcome measures

Outcome measures
Measure	Crinone n=18 Participants 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.	Crinone® Plus Duphaston n=29 Participants 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.
Early Abortion Rate	11.1 Percentage of participants Interval 1.4 to 34.7	13.8 Percentage of participants Interval 3.9 to 31.7

SECONDARY outcome

Timeframe: 2, 5 and 9 weeks after embryo transfer

Population: Safety analysis set included all participants who have received at least one dose of study intervention. Here, "Number of participants analyzed" signified those participants who had embryo transferred.

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.

Outcome measures

Outcome measures
Measure	Crinone n=85 Participants 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.	Crinone® Plus Duphaston n=86 Participants 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.
Luteal Phase Bleeding Rate	1.2 Percentage of participants Interval 0.0 to 6.4	3.5 Percentage of participants Interval 0.7 to 9.9

SECONDARY outcome

Timeframe: 5 and 9 weeks after embryo transfer

Population: Safety analysis set included all participants who have received at least one dose of study intervention. Here, "Number of participants analyzed" signified those participants who had embryo transferred.

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.

Outcome measures

Outcome measures
Measure	Crinone n=85 Participants 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.	Crinone® Plus Duphaston n=86 Participants 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.
Vaginal Bleeding Rate	7.1 Percentage of participants Interval 2.6 to 14.7	10.5 Percentage of participants Interval 4.9 to 18.9

Adverse Events

Crinone

Serious events: 4 serious events

Other events: 17 other events

Deaths: 0 deaths

Crinone® Plus Duphaston

Serious events: 4 serious events

Other events: 14 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Crinone n=86 participants at risk 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.	Crinone® Plus Duphaston n=86 participants at risk 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.
Injury, poisoning and procedural complications Decreased embryo viability	2.3% 2/86 • Day of endometrial transformation (Day -5) up to 12 weeks of pregnancy	2.3% 2/86 • Day of endometrial transformation (Day -5) up to 12 weeks of pregnancy
Pregnancy, puerperium and perinatal conditions Abortion incomplete	1.2% 1/86 • Day of endometrial transformation (Day -5) up to 12 weeks of pregnancy	0.00% 0/86 • Day of endometrial transformation (Day -5) up to 12 weeks of pregnancy
Pregnancy, puerperium and perinatal conditions Abortion spontaneous	0.00% 0/86 • Day of endometrial transformation (Day -5) up to 12 weeks of pregnancy	2.3% 2/86 • Day of endometrial transformation (Day -5) up to 12 weeks of pregnancy
Pregnancy, puerperium and perinatal conditions Ectopic pregnancy	1.2% 1/86 • Day of endometrial transformation (Day -5) up to 12 weeks of pregnancy	0.00% 0/86 • Day of endometrial transformation (Day -5) up to 12 weeks of pregnancy

Other adverse events

Other adverse events
Measure	Crinone n=86 participants at risk 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.	Crinone® Plus Duphaston n=86 participants at risk 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.
Pregnancy, puerperium and perinatal conditions Abortion threatened	9.3% 8/86 • Day of endometrial transformation (Day -5) up to 12 weeks of pregnancy	4.7% 4/86 • Day of endometrial transformation (Day -5) up to 12 weeks of pregnancy
Pregnancy, puerperium and perinatal conditions Biochemical pregnancy	9.3% 8/86 • Day of endometrial transformation (Day -5) up to 12 weeks of pregnancy	3.5% 3/86 • Day of endometrial transformation (Day -5) up to 12 weeks of pregnancy
Pregnancy, puerperium and perinatal conditions Vaginal haemorrhage	2.3% 2/86 • Day of endometrial transformation (Day -5) up to 12 weeks of pregnancy	8.1% 7/86 • Day of endometrial transformation (Day -5) up to 12 weeks of pregnancy

Additional Information

Communication Center

Merck KGaA, Darmstadt, Germany

Phone: +49-6151-72-5200

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place