Trial Outcomes & Findings for Clinical Trial Comparing Endometrial Transformation With Subcutaneous Progesterone Versus Intramuscular Progesterone (NCT NCT02567552)

Results Overview

Histologic dating of the endometrium at day 5: early secretory phase, media secretory phase or late secretory phase

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

24 participants

Primary outcome timeframe

5 days

Results posted on

2019-12-16

Participant Flow

Participant milestones

Participant milestones
Measure	Prolutex Subcutaneous progesterone Subcutaneous progesterone: subcutaneous progesterone 25 mg/day	Prontogest Intramuscular progesterone Intramuscular progesterone: intramuscular progesterone 50 mg/day
Overall Study STARTED	12	12
Overall Study COMPLETED	12	11
Overall Study NOT COMPLETED	0	1

Reasons for withdrawal

Reasons for withdrawal
Measure	Prolutex Subcutaneous progesterone Subcutaneous progesterone: subcutaneous progesterone 25 mg/day	Prontogest Intramuscular progesterone Intramuscular progesterone: intramuscular progesterone 50 mg/day
Overall Study Adverse Event	0	1

Baseline Characteristics

Clinical Trial Comparing Endometrial Transformation With Subcutaneous Progesterone Versus Intramuscular Progesterone

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Prolutex n=12 Participants Subcutaneous progesterone Subcutaneous progesterone: subcutaneous progesterone 25 mg/day	Prontogest n=12 Participants Intramuscular progesterone Intramuscular progesterone: intramuscular progesterone 50 mg/day	Total n=24 Participants Total of all reporting groups
Age, Continuous	26.92 years STANDARD_DEVIATION 5.32 • n=5 Participants	25.58 years STANDARD_DEVIATION 2.39 • n=7 Participants	26.25 years STANDARD_DEVIATION 4.09 • n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Body Mass Index	21.76 kg/m^2 STANDARD_DEVIATION 2.88 • n=5 Participants	23.12 kg/m^2 STANDARD_DEVIATION 2.79 • n=7 Participants	22.44 kg/m^2 STANDARD_DEVIATION 2.86 • n=5 Participants
Height	166.75 cm STANDARD_DEVIATION 5.10 • n=5 Participants	162.08 cm STANDARD_DEVIATION 3.50 • n=7 Participants	164.42 cm STANDARD_DEVIATION 4.90 • n=5 Participants
Weight	61.00 Kg STANDARD_DEVIATION 10.05 • n=5 Participants	61.00 Kg STANDARD_DEVIATION 8.55 • n=7 Participants	61.00 Kg STANDARD_DEVIATION 9.12 • n=5 Participants
Blood Progesterone Level	1.31 ng/ml STANDARD_DEVIATION 0.85 • n=5 Participants	1.44 ng/ml STANDARD_DEVIATION 0.77 • n=7 Participants	1.37 ng/ml STANDARD_DEVIATION 0.79 • n=5 Participants
Blood Estradiol Level	2020.35 pg/ml STANDARD_DEVIATION 998.36 • n=5 Participants	2464.33 pg/ml STANDARD_DEVIATION 1144.19 • n=7 Participants	2262.52 pg/ml STANDARD_DEVIATION 1078.94 • n=5 Participants
Blood LH level	1.25 pg/ml STANDARD_DEVIATION 0.45 • n=5 Participants	1.24 pg/ml STANDARD_DEVIATION 0.91 • n=7 Participants	1.25 pg/ml STANDARD_DEVIATION 0.70 • n=5 Participants
Endometrial Thickness	8.88 mm STANDARD_DEVIATION 1.98 • n=5 Participants	9.58 mm STANDARD_DEVIATION 1.61 • n=7 Participants	9.23 mm STANDARD_DEVIATION 1.80 • n=5 Participants

PRIMARY outcome

Timeframe: 5 days

Histologic dating of the endometrium at day 5: early secretory phase, media secretory phase or late secretory phase

Outcome measures

Outcome measures
Measure	Prolutex n=12 Participants Subcutaneous progesterone Subcutaneous progesterone: subcutaneous progesterone 25 mg/day	Prontogest n=11 Participants Intramuscular progesterone Intramuscular progesterone: intramuscular progesterone 50 mg/day
Predecidual Transformation early secretory phase	1 participants	2 participants
Predecidual Transformation media secretory phase	7 participants	8 participants
Predecidual Transformation late secretory phase	4 participants	1 participants

PRIMARY outcome

Timeframe: 5 days

Rate of transformation of endometrial stromal fibroblasts into specialized secretory decidual cells (three categories: less than 25%, between 26% and 50%, and over 50%)

Outcome measures

Outcome measures
Measure	Prolutex n=12 Participants Subcutaneous progesterone Subcutaneous progesterone: subcutaneous progesterone 25 mg/day	Prontogest n=11 Participants Intramuscular progesterone Intramuscular progesterone: intramuscular progesterone 50 mg/day
Decidualization of Stromal Cell <25% of stromal cell	3 participants	2 participants
Decidualization of Stromal Cell 25-50% of stromal cell	3 participants	7 participants
Decidualization of Stromal Cell > 50% of stromal cell	6 participants	2 participants

PRIMARY outcome

Timeframe: 5 days

Endometrial dating of luteal phase days according to the Noyes criteria

Outcome measures

Outcome measures
Measure	Prolutex n=12 Participants Subcutaneous progesterone Subcutaneous progesterone: subcutaneous progesterone 25 mg/day	Prontogest n=11 Participants Intramuscular progesterone Intramuscular progesterone: intramuscular progesterone 50 mg/day
Endometrial Maturation Using Noyes' Criteria	9.08 days Standard Deviation 2.23	7.64 days Standard Deviation 2.01

PRIMARY outcome

Timeframe: 5 days

Population: We assessed the gene expression of 238 endometrial genes to detect differences in gene expression between treatments. This analysis could not be performed in 1 patient of the prolutex group because of the poor quality of the sample collected

Gene expression profile of endometrial

Outcome measures

Outcome measures
Measure	Prolutex n=238 Endometrial genes Subcutaneous progesterone Subcutaneous progesterone: subcutaneous progesterone 25 mg/day	Prontogest n=238 Endometrial genes Intramuscular progesterone Intramuscular progesterone: intramuscular progesterone 50 mg/day
Endometrial Gene Expression differential expressed genes	28 Endometrial genes	28 Endometrial genes
Endometrial Gene Expression the same trend of gene expression	210 Endometrial genes	210 Endometrial genes

PRIMARY outcome

Timeframe: 5 days

Population: We assessed the expressed genes with a significantly high gene expression difference between treatments (adj-p-value \< 0.05, Fold Change\>3) This analysis could not be performed in 1 patient of the prolutex group because of the poor quality of the sample collected

Genes with a significantly high gene expression difference (adj-p-value \< 0.05, Fold Change\>3)

Outcome measures

Outcome measures
Measure	Prolutex n=238 Endometrial genes Subcutaneous progesterone Subcutaneous progesterone: subcutaneous progesterone 25 mg/day	Prontogest n=238 Endometrial genes Intramuscular progesterone Intramuscular progesterone: intramuscular progesterone 50 mg/day
Endometrial Gene Expression Difference expressed genes with fold change > 3	4 Endometrial genes	4 Endometrial genes
Endometrial Gene Expression Difference expressed genes without or with fold change < 3	234 Endometrial genes	234 Endometrial genes

SECONDARY outcome

Timeframe: 5 days

Endometrial thickness measurement by means of transvaginal ultrasound.

Outcome measures

Outcome measures
Measure	Prolutex n=12 Participants Subcutaneous progesterone Subcutaneous progesterone: subcutaneous progesterone 25 mg/day	Prontogest n=12 Participants Intramuscular progesterone Intramuscular progesterone: intramuscular progesterone 50 mg/day
Endometrial Thickness	8.46 mm Standard Deviation 2.66	9.61 mm Standard Deviation 1.24

SECONDARY outcome

Timeframe: day 0

Blood estradiol level on the day of follicular puncture

Outcome measures

Outcome measures
Measure	Prolutex n=12 Participants Subcutaneous progesterone Subcutaneous progesterone: subcutaneous progesterone 25 mg/day	Prontogest n=11 Participants Intramuscular progesterone Intramuscular progesterone: intramuscular progesterone 50 mg/day
Blood Estradiol Level	1384.06 pg/mL Standard Deviation 1122.80	1208.58 pg/mL Standard Deviation 502.96

SECONDARY outcome

Timeframe: day 0

Blood progesterone level on the day of follicular puncture

Outcome measures

Outcome measures
Measure	Prolutex n=12 Participants Subcutaneous progesterone Subcutaneous progesterone: subcutaneous progesterone 25 mg/day	Prontogest n=12 Participants Intramuscular progesterone Intramuscular progesterone: intramuscular progesterone 50 mg/day
Blood Progesterone Level	14.40 ng/mL Standard Deviation 6.63	10.92 ng/mL Standard Deviation 6.88

SECONDARY outcome

Timeframe: day 0

Blood Luteinizing hormone level on the day of follicular puncture

Outcome measures

Outcome measures
Measure	Prolutex n=12 Participants Subcutaneous progesterone Subcutaneous progesterone: subcutaneous progesterone 25 mg/day	Prontogest n=12 Participants Intramuscular progesterone Intramuscular progesterone: intramuscular progesterone 50 mg/day
Blood LH Level	2.32 pg/mL Standard Deviation 0.89	2.75 pg/mL Standard Deviation 2.08

SECONDARY outcome

Timeframe: 5 days

Blood estradiol level 5 days after progesterone treatment

Outcome measures

Outcome measures
Measure	Prolutex n=12 Participants Subcutaneous progesterone Subcutaneous progesterone: subcutaneous progesterone 25 mg/day	Prontogest n=11 Participants Intramuscular progesterone Intramuscular progesterone: intramuscular progesterone 50 mg/day
Blood Estradiol Level	257.88 pg/mL Standard Deviation 150.65	246.45 pg/mL Standard Deviation 106.90

SECONDARY outcome

Timeframe: 5 days

Blood progesterone level 5 days after progesterone treatment

Outcome measures

Outcome measures
Measure	Prolutex n=12 Participants Subcutaneous progesterone Subcutaneous progesterone: subcutaneous progesterone 25 mg/day	Prontogest n=11 Participants Intramuscular progesterone Intramuscular progesterone: intramuscular progesterone 50 mg/day
Blood Progesterone Level	3.16 ng/mL Standard Deviation 1.00	11.04 ng/mL Standard Deviation 5.21

SECONDARY outcome

Timeframe: 5 days

Blood Luteinizing hormone level 5 days after progesterone treatment

Outcome measures

Outcome measures
Measure	Prolutex n=12 Participants Subcutaneous progesterone Subcutaneous progesterone: subcutaneous progesterone 25 mg/day	Prontogest n=11 Participants Intramuscular progesterone Intramuscular progesterone: intramuscular progesterone 50 mg/day
Blood LH Level	1.30 pg/mL Standard Deviation 0.60	2.92 pg/mL Standard Deviation 5.36

SECONDARY outcome

Timeframe: 5 days

Number of Participants with side effects during the study"

Outcome measures

Outcome measures
Measure	Prolutex n=12 Participants Subcutaneous progesterone Subcutaneous progesterone: subcutaneous progesterone 25 mg/day	Prontogest n=12 Participants Intramuscular progesterone Intramuscular progesterone: intramuscular progesterone 50 mg/day
Number of Participants With Side Effects During the Study	5 participants	4 participants

Adverse Events

Prolutex

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Prontogest

Serious events: 0 serious events

Other events: 4 other events

Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Other adverse events
Measure	Prolutex n=12 participants at risk Subcutaneous progesterone Subcutaneous progesterone: subcutaneous progesterone 25 mg/day	Prontogest n=12 participants at risk Intramuscular progesterone Intramuscular progesterone: intramuscular progesterone 50 mg/day
General disorders Pain in injection site	0.00% 0/12 • 5 days	33.3% 4/12 • Number of events 6 • 5 days
General disorders Discomfort in injection site	25.0% 3/12 • Number of events 6 • 5 days	0.00% 0/12 • 5 days
Reproductive system and breast disorders Breast inflammation	16.7% 2/12 • Number of events 2 • 5 days	0.00% 0/12 • 5 days

Additional Information

Evelin Lara Molina

IVI Barcelona

Phone: +34 93 531 63 00

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place