Trial Outcomes & Findings for Ovulation Induction in Women With Clomiphene Citrate Resistant PCOS (NCT NCT01909141)
NCT ID: NCT01909141
Last Updated: 2015-10-20
Results Overview
Recruitment status
COMPLETED
Study phase
EARLY_PHASE1
Target enrollment
100 participants
Primary outcome timeframe
3 months
Results posted on
2015-10-20
Participant Flow
Participant milestones
| Measure |
Arm 1:Letrozole-pioglitazone -Metformin Group
Arm 1 received letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days.
induction of ovulation using letrozole-pioglitazone-metformin: induction of ovulation was done for arm 1 for 3 consecutive cycles unless pregnancy occurred.
transvaginal ultrasound: transvaginal ultrasound will be done starting from day 10 and every 48 hours until finding a follicle of \> 18 mm or till day 20 of the cycle
body mass index (BMI) calculation: BMI was calculated.
day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women.
serum estradiol (E2) was done on day of hCG administration for all women.
serum progesterone on day 21 was done for all women.
|
Arm 2: Clomiphene Citrate-pioglitazone-metformin
Arm 2 received clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days.
induction of ovulation using clomiphene citrate-pioglitazone-metformin: induction of ovulation for arm 2 was done in 3 consecutive cycles unless pregnancy occurred.
transvaginal ultrasound: transvaginal ultrasound was done starting from day 10 and every 48 hours until finding a follicle of \> 18 mm or till day 20 of the cycle
body mass index (BMI) calculation: BMI was calculated.
day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women.
serum estradiol (E2) was done on day of hCG administration for all women.
serum progesterone on day 21 was done for all women.
|
|---|---|---|
|
Overall Study
STARTED
|
50
|
50
|
|
Overall Study
COMPLETED
|
50
|
50
|
|
Overall Study
NOT COMPLETED
|
0
|
0
|
Reasons for withdrawal
Withdrawal data not reported
Baseline Characteristics
Ovulation Induction in Women With Clomiphene Citrate Resistant PCOS
Baseline characteristics by cohort
| Measure |
Arm 1:Letrozole-pioglitazone -Metformin Group
n=50 Participants
Arm 1 received letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days.
induction of ovulation using letrozole-pioglitazone-metformin: induction of ovulation was done for arm 1 for 3 consecutive cycles unless pregnancy occurred.
transvaginal ultrasound: transvaginal ultrasound was done starting from day 10 and every 48 hours until finding a follicle of \> 18 mm or till day 20 of the cycle
body mass index (BMI) calculation: BMI was calculated.
day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women.
serum estradiol (E2) was done on day of hCG administration for all women.
serum progesterone on day 21 was done for all women.
|
Arm 2: Clomiphene Citrate-pioglitazone-metformin
n=50 Participants
Arm 2 will received clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days.
induction of ovulation using clomiphene citrate-pioglitazone-metformin: induction of ovulation for arm 2 was done in 3 consecutive cycles unless pregnancy occured.
transvaginal ultrasound: transvaginal ultrasound was done starting from day 10 and every 48 hours until finding a follicle of \> 18 mm or till day 20 of the cycle
body mass index (BMI) calculation: BMI was calculated.
day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women.
serum estradiol (E2) was done on day of hCG administration for all women.
serum progesterone on day 21 was done for all women.
|
Total
n=100 Participants
Total of all reporting groups
|
|---|---|---|---|
|
Age, Continuous
|
25.8 years
STANDARD_DEVIATION 3.62 • n=5 Participants
|
26.58 years
STANDARD_DEVIATION 2.9 • n=7 Participants
|
26.19 years
STANDARD_DEVIATION 3.29 • n=5 Participants
|
|
Sex: Female, Male
Female
|
50 Participants
n=5 Participants
|
50 Participants
n=7 Participants
|
100 Participants
n=5 Participants
|
|
Sex: Female, Male
Male
|
0 Participants
n=5 Participants
|
0 Participants
n=7 Participants
|
0 Participants
n=5 Participants
|
|
Region of Enrollment
Egypt
|
50 participants
n=5 Participants
|
50 participants
n=7 Participants
|
100 participants
n=5 Participants
|
|
infertility period
|
2.67 years
STANDARD_DEVIATION 1.62 • n=5 Participants
|
3.07 years
STANDARD_DEVIATION 1.46 • n=7 Participants
|
2.87 years
STANDARD_DEVIATION 1.5 • n=5 Participants
|
|
BMI
|
26.45 kg/m^2
STANDARD_DEVIATION 2.84 • n=5 Participants
|
26.57 kg/m^2
STANDARD_DEVIATION 2.7 • n=7 Participants
|
26.51 kg/m^2
STANDARD_DEVIATION 2.75 • n=5 Participants
|
|
waist/hip ratio
|
0.838 ratio
STANDARD_DEVIATION 0.02 • n=5 Participants
|
0.837 ratio
STANDARD_DEVIATION 0.04 • n=7 Participants
|
0.837 ratio
STANDARD_DEVIATION 0.037 • n=5 Participants
|
|
systolic blood pressure
|
106.08 mmHg
STANDARD_DEVIATION 8.81 • n=5 Participants
|
107.04 mmHg
STANDARD_DEVIATION 8.97 • n=7 Participants
|
106.56 mmHg
STANDARD_DEVIATION 8.86 • n=5 Participants
|
|
diastolic blood pressure
|
69.6 mmHg
STANDARD_DEVIATION 5.31 • n=5 Participants
|
68.44 mmHg
STANDARD_DEVIATION 5.89 • n=7 Participants
|
69.02 mmHg
STANDARD_DEVIATION 5.61 • n=5 Participants
|
|
hirsutism
|
11 participants
n=5 Participants
|
10 participants
n=7 Participants
|
21 participants
n=5 Participants
|
|
acne
|
7 participants
n=5 Participants
|
4 participants
n=7 Participants
|
11 participants
n=5 Participants
|
|
ovarian volume
|
14.17 ml
STANDARD_DEVIATION 0.76 • n=5 Participants
|
14.58 ml
STANDARD_DEVIATION 1.42 • n=7 Participants
|
14.19 ml
STANDARD_DEVIATION 0.98 • n=5 Participants
|
|
FSH
|
5.71 mIU/L
STANDARD_DEVIATION 1.34 • n=5 Participants
|
5.68 mIU/L
STANDARD_DEVIATION 1.38 • n=7 Participants
|
5.7 mIU/L
STANDARD_DEVIATION 1.35 • n=5 Participants
|
|
LH
|
9.81 mIU/L
STANDARD_DEVIATION 3.16 • n=5 Participants
|
10.55 mIU/L
STANDARD_DEVIATION 3.25 • n=7 Participants
|
10.18 mIU/L
STANDARD_DEVIATION 3.21 • n=5 Participants
|
|
E2
|
49.83 Pmol/dL
STANDARD_DEVIATION 7.31 • n=5 Participants
|
47.75 Pmol/dL
STANDARD_DEVIATION 10.02 • n=7 Participants
|
48.24 Pmol/dL
STANDARD_DEVIATION 8.56 • n=5 Participants
|
|
prolactin
|
15.52 ng/ml
STANDARD_DEVIATION 4.84 • n=5 Participants
|
14.3 ng/ml
STANDARD_DEVIATION 5.6 • n=7 Participants
|
14.9 ng/ml
STANDARD_DEVIATION 5.24 • n=5 Participants
|
|
total testosterone
|
1.19 nmol/L
STANDARD_DEVIATION 0.25 • n=5 Participants
|
1.13 nmol/L
STANDARD_DEVIATION 0.2 • n=7 Participants
|
1.16 nmol/L
STANDARD_DEVIATION 0.23 • n=5 Participants
|
|
free testosterone
|
3.87 Pmol/dL
STANDARD_DEVIATION 0.61 • n=5 Participants
|
4.12 Pmol/dL
STANDARD_DEVIATION 1.17 • n=7 Participants
|
3.99 Pmol/dL
STANDARD_DEVIATION 0.94 • n=5 Participants
|
|
TSH
|
3.42 mIU/L
STANDARD_DEVIATION 0.61 • n=5 Participants
|
3.51 mIU/L
STANDARD_DEVIATION 0.44 • n=7 Participants
|
3.47 mIU/L
STANDARD_DEVIATION 0.53 • n=5 Participants
|
|
free T4
|
13.78 nmol/L
STANDARD_DEVIATION 0.84 • n=5 Participants
|
13.58 nmol/L
STANDARD_DEVIATION 0.45 • n=7 Participants
|
13.68 nmol/L
STANDARD_DEVIATION 0.68 • n=5 Participants
|
PRIMARY outcome
Timeframe: 3 monthsOutcome measures
| Measure |
Arm 1:Letrozole-pioglitazone -Metformin Group
n=50 Participants
Arm 1 receivde letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days.
induction of ovulation using letrozole-pioglitazone-metformin: induction of ovulation was be done for arm 1 for 3 consecutive cycles unless pregnancy occured.
transvaginal ultrasound: transvaginal ultrasound was done starting from day 10 and every 48 hours until finding a follicle of \> 18 mm or till day 20 of the cycle
body mass index (BMI) calculation: BMI was caculated.
day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women.
serum estradiol (E2) was done on day of hCG administration for all women.
serum progesterone on day 21 was done for all women.
|
Arm 2: Clomiphene Citrate-pioglitazone-metformin
n=50 Participants
Arm 2 received clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days.
induction of ovulation using clomiphene citrate-pioglitazone-metformin: induction of ovulation for arm 2 was done in 3 consecutive cycles unless pregnancy occured.
transvaginal ultrasound: transvaginal ultrasound was done starting from day 10 and every 48 hours until finding a follicle of \> 18 mm or till day 20 of the cycle
body mass index (BMI) calculation: BMI was calculated
day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women.
serum estradiol (E2) was done on day of hCG administration for all women.
serum progesterone on day 21 was done for all women.
|
|---|---|---|
|
Ovulation Rate
|
93 percentage of all cycles
|
108 percentage of all cycles
|
SECONDARY outcome
Timeframe: 3 monthsOutcome measures
| Measure |
Arm 1:Letrozole-pioglitazone -Metformin Group
n=50 Participants
Arm 1 receivde letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days.
induction of ovulation using letrozole-pioglitazone-metformin: induction of ovulation was be done for arm 1 for 3 consecutive cycles unless pregnancy occured.
transvaginal ultrasound: transvaginal ultrasound was done starting from day 10 and every 48 hours until finding a follicle of \> 18 mm or till day 20 of the cycle
body mass index (BMI) calculation: BMI was caculated.
day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women.
serum estradiol (E2) was done on day of hCG administration for all women.
serum progesterone on day 21 was done for all women.
|
Arm 2: Clomiphene Citrate-pioglitazone-metformin
n=50 Participants
Arm 2 received clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days.
induction of ovulation using clomiphene citrate-pioglitazone-metformin: induction of ovulation for arm 2 was done in 3 consecutive cycles unless pregnancy occured.
transvaginal ultrasound: transvaginal ultrasound was done starting from day 10 and every 48 hours until finding a follicle of \> 18 mm or till day 20 of the cycle
body mass index (BMI) calculation: BMI was calculated
day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women.
serum estradiol (E2) was done on day of hCG administration for all women.
serum progesterone on day 21 was done for all women.
|
|---|---|---|
|
Number of Follicles>18mm.
|
1.44 follicles
Standard Deviation 0.16
|
1.5 follicles
Standard Deviation 0.86
|
SECONDARY outcome
Timeframe: 3 monthsOutcome measures
| Measure |
Arm 1:Letrozole-pioglitazone -Metformin Group
n=50 Participants
Arm 1 receivde letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days.
induction of ovulation using letrozole-pioglitazone-metformin: induction of ovulation was be done for arm 1 for 3 consecutive cycles unless pregnancy occured.
transvaginal ultrasound: transvaginal ultrasound was done starting from day 10 and every 48 hours until finding a follicle of \> 18 mm or till day 20 of the cycle
body mass index (BMI) calculation: BMI was caculated.
day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women.
serum estradiol (E2) was done on day of hCG administration for all women.
serum progesterone on day 21 was done for all women.
|
Arm 2: Clomiphene Citrate-pioglitazone-metformin
n=50 Participants
Arm 2 received clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days.
induction of ovulation using clomiphene citrate-pioglitazone-metformin: induction of ovulation for arm 2 was done in 3 consecutive cycles unless pregnancy occured.
transvaginal ultrasound: transvaginal ultrasound was done starting from day 10 and every 48 hours until finding a follicle of \> 18 mm or till day 20 of the cycle
body mass index (BMI) calculation: BMI was calculated
day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women.
serum estradiol (E2) was done on day of hCG administration for all women.
serum progesterone on day 21 was done for all women.
|
|---|---|---|
|
Endometrial Thickness
|
10.56 mm
Standard Deviation 1.79
|
9.68 mm
Standard Deviation 1.39
|
SECONDARY outcome
Timeframe: 3 monthsOutcome measures
| Measure |
Arm 1:Letrozole-pioglitazone -Metformin Group
n=50 Participants
Arm 1 receivde letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days.
induction of ovulation using letrozole-pioglitazone-metformin: induction of ovulation was be done for arm 1 for 3 consecutive cycles unless pregnancy occured.
transvaginal ultrasound: transvaginal ultrasound was done starting from day 10 and every 48 hours until finding a follicle of \> 18 mm or till day 20 of the cycle
body mass index (BMI) calculation: BMI was caculated.
day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women.
serum estradiol (E2) was done on day of hCG administration for all women.
serum progesterone on day 21 was done for all women.
|
Arm 2: Clomiphene Citrate-pioglitazone-metformin
n=50 Participants
Arm 2 received clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days.
induction of ovulation using clomiphene citrate-pioglitazone-metformin: induction of ovulation for arm 2 was done in 3 consecutive cycles unless pregnancy occured.
transvaginal ultrasound: transvaginal ultrasound was done starting from day 10 and every 48 hours until finding a follicle of \> 18 mm or till day 20 of the cycle
body mass index (BMI) calculation: BMI was calculated
day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women.
serum estradiol (E2) was done on day of hCG administration for all women.
serum progesterone on day 21 was done for all women.
|
|---|---|---|
|
Pregnancy Rate
|
28 participants
|
24 participants
|
OTHER_PRE_SPECIFIED outcome
Timeframe: 3 monthsserum creatinine was measured at the end of the study period (after 3 months) in both groups.
Outcome measures
| Measure |
Arm 1:Letrozole-pioglitazone -Metformin Group
n=50 Participants
Arm 1 receivde letrozole 2.5 mg/day starting from the 3rd day of the cycle and for 5 days and (combined pioglitazone 15 mg+ metformin 850 mg) once daily from the first day of the cycle for 10 days.
induction of ovulation using letrozole-pioglitazone-metformin: induction of ovulation was be done for arm 1 for 3 consecutive cycles unless pregnancy occured.
transvaginal ultrasound: transvaginal ultrasound was done starting from day 10 and every 48 hours until finding a follicle of \> 18 mm or till day 20 of the cycle
body mass index (BMI) calculation: BMI was caculated.
day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women.
serum estradiol (E2) was done on day of hCG administration for all women.
serum progesterone on day 21 was done for all women.
|
Arm 2: Clomiphene Citrate-pioglitazone-metformin
n=50 Participants
Arm 2 received clomiphene citrate 100 mg/day starting from the 3rd day of the cycle for 5 days and (combined pioglitazone 15 mg + metformin 850 mg) once daily from the first day of the cycle for 10 days.
induction of ovulation using clomiphene citrate-pioglitazone-metformin: induction of ovulation for arm 2 was done in 3 consecutive cycles unless pregnancy occured.
transvaginal ultrasound: transvaginal ultrasound was done starting from day 10 and every 48 hours until finding a follicle of \> 18 mm or till day 20 of the cycle
body mass index (BMI) calculation: BMI was calculated
day 3: follicle stimulating hormone (FSH), luteinizing hormone (LH), thyroid stimulating hormone (TSH), total testosterone: baseline hormonal assay (day 3 FSH, LH, TSH and total testosterone) were done for all women.
serum estradiol (E2) was done on day of hCG administration for all women.
serum progesterone on day 21 was done for all women.
|
|---|---|---|
|
Safety of Pioglitazone as Regards Serum Creatinine
|
0.62 mg/dL
Standard Deviation 0.04
|
0.57 mg/dL
Standard Deviation 0.03
|
Adverse Events
Arm 1:Letrozole-pioglitazone -Metformin Group
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Arm 2: Clomiphene Citrate-pioglitazone-metformin
Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths
Serious adverse events
Adverse event data not reported
Other adverse events
Adverse event data not reported
Additional Information
Results disclosure agreements
- Principal investigator is a sponsor employee
- Publication restrictions are in place