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Pregnancy in Polycystic Ovary Syndrome II (PPCOSII)

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ClinicalTrials.gov Identifier: NCT00719186
Recruitment Status : Completed
First Posted : July 21, 2008
Results First Posted : June 9, 2014
Last Update Posted : June 14, 2018
Sponsor:
Collaborators:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Penn State University
University of Colorado, Denver
University of Michigan
University of Pennsylvania
The University of Texas Health Science Center at San Antonio
University of Vermont
Wayne State University
Information provided by (Responsible Party):
Heping Zhang, Yale University

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor);   Primary Purpose: Treatment
Conditions Pregnancy
Polycystic Ovary Syndrome
Interventions Drug: Clomiphene citrate
Drug: Letrozole
Enrollment 750
Recruitment Details  
Pre-assignment Details  
Arm/Group Title Arm A: Clomiphene Citrate Arm B: Letrozole
Hide Arm/Group Description

Clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Clomiphene citrate: Clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Letrozole 2.5 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Letrozole: Letrozole 2.5 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Period Title: Overall Study
Started 376 374
Completed 376 374
Not Completed 0 0
Arm/Group Title Arm A: Clomiphene Citrate Arm B: Letrozole Total
Hide Arm/Group Description

Clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Clomiphene citrate: Clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Letrozole 2.5 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Letrozole: Letrozole 2.5 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Total of all reporting groups
Overall Number of Baseline Participants 376 374 750
Hide Baseline Analysis Population Description
[Not Specified]
Age, Continuous  
Mean (Standard Deviation)
Unit of measure:  Years
Number Analyzed 376 participants 374 participants 750 participants
28.2  (4.0) 28.9  (4.5) 28.9  (4.3)
Age, Categorical  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 376 participants 374 participants 750 participants
<=18 years
0
   0.0%
0
   0.0%
0
   0.0%
Between 18 and 65 years
376
 100.0%
374
 100.0%
750
 100.0%
>=65 years
0
   0.0%
0
   0.0%
0
   0.0%
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 376 participants 374 participants 750 participants
Female
376
 100.0%
374
 100.0%
750
 100.0%
Male
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Count of Participants
Unit of measure:  Participants
United States Number Analyzed 376 participants 374 participants 750 participants
376
 100.0%
374
 100.0%
750
 100.0%
1.Primary Outcome
Title Live Birth
Hide Description The primary outcome measure is the occurrence of a live birth during the study period. Safety measures will be the number and type of reported adverse events in subjects and offspring.
Time Frame as few as 5 months, up to 16 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm A: Clomiphene Citrate Arm B: Letrozole
Hide Arm/Group Description:

Clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Clomiphene citrate: Clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Letrozole 2.5 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Letrozole: Letrozole 2.5 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Overall Number of Participants Analyzed 376 374
Measure Type: Count of Participants
Unit of Measure: Participants
72
  19.1%
103
  27.5%
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection Arm A: Clomiphene Citrate, Arm B: Letrozole
Comments [Not Specified]
Type of Statistical Test Superiority or Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.007
Comments [Not Specified]
Method Chi-squared
Comments [Not Specified]
2.Secondary Outcome
Title Number of Pregnancy
Hide Description [Not Specified]
Time Frame as few as 5 months, up to 16 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm A: Clomiphene Citrate Arm B: Letrozole
Hide Arm/Group Description:

Clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Clomiphene citrate: Clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Letrozole 2.5 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Letrozole: Letrozole 2.5 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Overall Number of Participants Analyzed 376 374
Measure Type: Count of Participants
Unit of Measure: Participants
103
  27.4%
154
  41.2%
3.Secondary Outcome
Title Number of Ovulations
Hide Description [Not Specified]
Time Frame as few as 5 months, up to 16 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm A: Clomiphene Citrate Arm B: Letrozole
Hide Arm/Group Description:

Clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Clomiphene citrate: Clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Letrozole 2.5 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Letrozole: Letrozole 2.5 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Overall Number of Participants Analyzed 376 374
Measure Type: Number
Unit of Measure: ovulations
331 388
4.Secondary Outcome
Title Number of Serious Adverse Events
Hide Description [Not Specified]
Time Frame as few as 5 months, up to 16 months
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title Arm A: Clomiphene Citrate Arm B: Letrozole
Hide Arm/Group Description:

Clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Clomiphene citrate: Clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Letrozole 2.5 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Letrozole: Letrozole 2.5 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Overall Number of Participants Analyzed 376 374
Measure Type: Number
Unit of Measure: events
13 22
5.Secondary Outcome
Title Neonatal Complication Rate
Hide Description [Not Specified]
Time Frame September 2008 - December 2011
Show Outcome Measure DataHide Outcome Measure Data
Hide Analysis Population Description
Neonatal complications reported per infant, an infant could have more than one complication.
Arm/Group Title Arm A: Clomiphene Citrate Arm B: Letrozole
Hide Arm/Group Description:

Clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Clomiphene citrate: Clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Letrozole 2.5 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Letrozole: Letrozole 2.5 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Overall Number of Participants Analyzed 66 102
Measure Type: Number
Unit of Measure: participants
Neonatal jaundice 17 27
Neonatal respiratory distress syndrome 2 7
Neonatal hospitalization >3 days 4 4
Intrauterine growth restriction 1 5
Neonatal infectin 2 2
Minor birth defect 0 1
Other complication 4 5
Congenital anomaly 1 4
Neonatal death 2 1
Time Frame 4 years
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title Arm A: Clomiphene Citrate Arm B: Letrozole
Hide Arm/Group Description

Clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Clomiphene citrate: Clomiphene citrate 50 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Letrozole 2.5 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

Letrozole: Letrozole 2.5 mg every day for 5 days (day 3-7 of cycle), for a total of 5 cycles or 20 weeks

All-Cause Mortality
Arm A: Clomiphene Citrate Arm B: Letrozole
Affected / at Risk (%) Affected / at Risk (%)
Total   --/--   --/-- 
Show Serious Adverse Events Hide Serious Adverse Events
Arm A: Clomiphene Citrate Arm B: Letrozole
Affected / at Risk (%) Affected / at Risk (%)
Total   13/376 (3.46%)   21/374 (5.61%) 
Congenital, familial and genetic disorders     
Congenital Anomaly  1/376 (0.27%)  4/374 (1.07%) 
Gastrointestinal disorders     
Appendectomy  0/376 (0.00%)  1/374 (0.27%) 
General disorders     
Hospitalization  3/376 (0.80%)  5/374 (1.34%) 
Hepatobiliary disorders     
cholecystectomy  1/376 (0.27%)  1/374 (0.27%) 
Cholecystitis  0/376 (0.00%)  1/374 (0.27%) 
Pregnancy, puerperium and perinatal conditions     
Fetal Demise  1/376 (0.27%)  1/374 (0.27%) 
Neonatal death  2/376 (0.53%)  1/374 (0.27%) 
Renal and urinary disorders     
Mid ureteral stone  0/376 (0.00%)  1/374 (0.27%) 
Reproductive system and breast disorders     
Ovarian torsion  1/376 (0.27%)  0/374 (0.00%) 
Ectopic Pregnancy  3/376 (0.80%)  4/374 (1.07%) 
Ruptured Corpus Luteum Cyst  0/376 (0.00%)  1/374 (0.27%) 
Heterotopic Pregnancy  1/376 (0.27%)  0/374 (0.00%) 
Pregnancy of Unknown Location  1/376 (0.27%)  1/374 (0.27%) 
Skin and subcutaneous tissue disorders     
Carcinoma of the Skin-stage 3  1/376 (0.27%)  0/374 (0.00%) 
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 2%
Arm A: Clomiphene Citrate Arm B: Letrozole
Affected / at Risk (%) Affected / at Risk (%)
Total   283/355 (79.72%)   285/359 (79.39%) 
Endocrine disorders     
Hot flashes  117/355 (32.96%)  73/359 (20.33%) 
Eye disorders     
Blurred vision  4/355 (1.13%)  8/359 (2.23%) 
Gastrointestinal disorders     
Nausea  91/355 (25.63%)  110/359 (30.64%) 
Dyspepsia  62/355 (17.46%)  45/359 (12.53%) 
Abdominal bloating  42/355 (11.83%)  49/359 (13.65%) 
Diarrhea  18/355 (5.07%)  24/359 (6.69%) 
Vomiting  20/355 (5.63%)  21/359 (5.85%) 
Constipation  20/355 (5.63%)  17/359 (4.74%) 
General disorders     
Fatigue  53/355 (14.93%)  78/359 (21.73%) 
Chills  8/355 (2.25%)  4/359 (1.11%) 
First Trimester other complication during pregnancy  8/355 (2.25%)  15/359 (4.18%) 
Hepatobiliary disorders     
Neonatal Jaundice  17/355 (4.79%)  27/359 (7.52%) 
Infections and infestations     
Upper respiratory infection  31/355 (8.73%)  38/359 (10.58%) 
Flu like symptoms  18/355 (5.07%)  29/359 (8.08%) 
Vaginal infection  16/355 (4.51%)  8/359 (2.23%) 
Allergic rhinitis  12/355 (3.38%)  10/359 (2.79%) 
fever  9/355 (2.54%)  13/359 (3.62%) 
Urinary tract infection  10/355 (2.82%)  12/359 (3.34%) 
Post-partum Infection  2/355 (0.56%)  7/359 (1.95%) 
Musculoskeletal and connective tissue disorders     
abdominal/pelvic pain  138/355 (38.87%)  146/359 (40.67%) 
Back pain  55/355 (15.49%)  64/359 (17.83%) 
Joint/limb pain  26/355 (7.32%)  33/359 (9.19%) 
Myalgia  9/355 (2.54%)  10/359 (2.79%) 
Nervous system disorders     
Headache  170/355 (47.89%)  167/359 (46.52%) 
Dizziness  27/355 (7.61%)  44/359 (12.26%) 
Pregnancy, puerperium and perinatal conditions     
Second Trimester Hyperemesis  5/355 (1.41%)  8/359 (2.23%) 
Second Trimester Gestational Diabetes  13/355 (3.66%)  27/359 (7.52%) 
Second Trimester Pre-eclampsia/ eclampsia  13/355 (3.66%)  18/359 (5.01%) 
Second Trimester pretem labor  12/355 (3.38%)  14/359 (3.90%) 
Second Trimester Premature rupture of membrane  7/355 (1.97%)  8/359 (2.23%) 
Second Trimester Incompetant cervix  6/355 (1.69%)  8/359 (2.23%) 
Post-partum hemorrhage  3/355 (0.85%)  8/359 (2.23%) 
Psychiatric disorders     
Agitation  37/355 (10.42%)  43/359 (11.98%) 
Irritability  33/355 (9.30%)  33/359 (9.19%) 
Insomnia  14/355 (3.94%)  12/359 (3.34%) 
Depression  10/355 (2.82%)  6/359 (1.67%) 
Renal and urinary disorders     
Urinary frequency  8/355 (2.25%)  7/359 (1.95%) 
Reproductive system and breast disorders     
Breast pain  76/355 (21.41%)  76/359 (21.17%) 
Dysmenorrhea  64/355 (18.03%)  60/359 (16.71%) 
Abnormal vaginal bleeding  9/355 (2.54%)  18/359 (5.01%) 
Vaginal discharge  4/355 (1.13%)  9/359 (2.51%) 
Respiratory, thoracic and mediastinal disorders     
Sinus complaints  4/355 (1.13%)  8/359 (2.23%) 
Neonatal respiratory distress syndrome  2/355 (0.56%)  7/359 (1.95%) 
Skin and subcutaneous tissue disorders     
Acne/ oily skin  24/355 (6.76%)  16/359 (4.46%) 
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Heping Zhang
Organization: Yale University
Phone: 203-785-5185
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: Heping Zhang, Yale University
ClinicalTrials.gov Identifier: NCT00719186     History of Changes
Other Study ID Numbers: RMN-PPCOSII
First Submitted: July 17, 2008
First Posted: July 21, 2008
Results First Submitted: March 25, 2014
Results First Posted: June 9, 2014
Last Update Posted: June 14, 2018