Ignite Creation Date:
2024-05-05 @ 7:39 PM
Last Modification Date:
2024-10-26 @ 9:52 AM
Study NCT ID:
NCT00719186
Status:
COMPLETED
Last Update Posted:
2018-06-14
First Post:
2008-07-17
Brief Title:
Pregnancy in Polycystic Ovary Syndrome II
Sponsor:
Yale University
Organization:
Yale University
Study Overview
Official Title:
A 20 Week Double-Blind Randomized Trial of Clomiphene Citrate and Letrozole for the Treatment of Infertility in Women With Polycystic Ovary Syndrome
Status:
COMPLETED
Status Verified Date:
2018-05
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
PPCOSII
Brief Summary:
The primary research hypothesis is that ovulation induction with an aromatase inhibitor letrozole is more likely to result in live birth than ovulation induction with a selective estrogen receptor modulator clomiphene citrate in infertile women with PCOS A safety hypothesis will also be incorporated into the primary research hypothesis in which we hypothesize both treatments are equally safe for mother and child
Secondary research hypotheses include
1 Treatment with letrozole is more likely to result in singleton pregnancy compared to treatment with clomiphene citrate Singleton pregnancy is defined as presence of a single intrauterine gestational sac with a single fetal pole and observable heart motion
2 Treatment with letrozole will less likely result in a first trimester intrauterine fetal demise than treatment with clomiphene citrate A first trimester IUFD is defined as a pregnancy that ends before 13 weeks gestation
3 Treatment with letrozole is more likely to result in ovulation increased ovulation rate compared to treatment with clomiphene citrate Ovulation is defined as a midluteal progesterone level 3 ngmL
4 The shortest time to pregnancy will be with letrozole
5 Age body mass index SHBG testosterone LH Anti-Mullerian Hormone AMH and degree of hirsutism and acne will be significant predictors of ovulation and conception regardless of treatment
6 Improvement in SHBG testosterone AMH and LH levels will be significant predictors of ovulation and conception regardless of treatment
7 DNA polymorphisms in estrogen action genes will predict response to study drug
8 Quality of Life will be better on letrozole than clomiphene
9 Letrozole will be more cost effective at achieving singleton pregnancies than clomiphene
Secondary research hypotheses include
1 Treatment with letrozole is more likely to result in singleton pregnancy compared to treatment with clomiphene citrate Singleton pregnancy is defined as presence of a single intrauterine gestational sac with a single fetal pole and observable heart motion
2 Treatment with letrozole will less likely result in a first trimester intrauterine fetal demise than treatment with clomiphene citrate A first trimester IUFD is defined as a pregnancy that ends before 13 weeks gestation
3 Treatment with letrozole is more likely to result in ovulation increased ovulation rate compared to treatment with clomiphene citrate Ovulation is defined as a midluteal progesterone level 3 ngmL
4 The shortest time to pregnancy will be with letrozole
5 Age body mass index SHBG testosterone LH Anti-Mullerian Hormone AMH and degree of hirsutism and acne will be significant predictors of ovulation and conception regardless of treatment
6 Improvement in SHBG testosterone AMH and LH levels will be significant predictors of ovulation and conception regardless of treatment
7 DNA polymorphisms in estrogen action genes will predict response to study drug
8 Quality of Life will be better on letrozole than clomiphene
9 Letrozole will be more cost effective at achieving singleton pregnancies than clomiphene
Detailed Description:
Preliminary data are promising for the use of letrozole to induce ovulation in infertile women with PCOS However the true magnitude of the effect of letrozole is difficult to discern from prior studies Therefore we intend to determine the safety and efficacy of letrozole an aromatase inhibitor compared to clomiphene citrate a selective estrogen receptor modulator in achieving live birth in infertile women with PCOS
Treatment- After progestin withdrawal 750 women will be equally randomized to two different treatment arms A clomiphene citrate 50 mg every day for 5 days day 3-7 of cycle or B letrozole 25 mg every day for 5 days day 3-7 of cycle for a total of 5 cycles or 20 weeks Dose will be increased in subsequent cycles in both treatment groups for non-response or poor ovulatory response up to a maximum of 150 mg of clomiphene a day x 5 days or 75 mg of letrozole a day x 5 days
Statistical Analysis- The primary analysis will use an intent-to-treat approach to examine differences in the live birth rate in the two treatment arms
Anticipated time to completion- A total of 4 years will be required to complete the study after start up 31 month enrollment period 5 month treatment period with 9 month additional observation to determine pregnancy outcomes This will be accomplished by enrolling 345 women with PCOS per center per month over the enrollment period N 7 RMN sites
Treatment- After progestin withdrawal 750 women will be equally randomized to two different treatment arms A clomiphene citrate 50 mg every day for 5 days day 3-7 of cycle or B letrozole 25 mg every day for 5 days day 3-7 of cycle for a total of 5 cycles or 20 weeks Dose will be increased in subsequent cycles in both treatment groups for non-response or poor ovulatory response up to a maximum of 150 mg of clomiphene a day x 5 days or 75 mg of letrozole a day x 5 days
Statistical Analysis- The primary analysis will use an intent-to-treat approach to examine differences in the live birth rate in the two treatment arms
Anticipated time to completion- A total of 4 years will be required to complete the study after start up 31 month enrollment period 5 month treatment period with 9 month additional observation to determine pregnancy outcomes This will be accomplished by enrolling 345 women with PCOS per center per month over the enrollment period N 7 RMN sites
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
None
Is a FDA Regulated Device?:
None
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
None
Is an FDA AA801 Violation?:
None