Randomized Controlled Trial of Combined Letrozole and Clomid (CLC II) Versus Letrozole Alone for Women With Anovulation

NCT05206448 | Active Not Recruiting Phase 4 Results DMC FDA Drug

• 1 other identifier: 201906826
• Study Type: interventional
• Target: 190
• Locations: 1 country
• Sites: 4

Brief Summary

This study evaluates the addition of clomiphene citrate (CC) to letrozole for the treatment of infertility in women with polycystic ovary syndrome across a course of two treatment cycles with stair step dosing of letrozole similar to standard of care. Half of the participants will receive letrozole and CC in combination, while the other half will receive letrozole alone.

Conditions

Polycystic Ovary Syndrome; PCOS; Infertility

Outcome Measures

Primary Outcomes (1)

• Ovulation

  Number of Participants with Mid-luteal serum progesterone level \>=3 ng/ml Number of cycles with Mid-luteal serum progesterone level \>=3 ng/ml

  Tested 6 to 8 days following patient reporting a positive ovulation test (LH surge). If no surge is detected, progesterone lab will be drawn on Cycle day 21-24.

Secondary Outcomes (12)

• Number of Corpora Lutea

  Cycle day 21-24 of 1st treatment cycle

• Number of Corpora Lutea

  Cycle day 21-24 of 2nd treatment cycle

• Number of Corpora Lutea

  Cycle day 21-24 of 3rd treatment cycle

• Endometrial Thickness

  Cycle day 21-24 of 1st treatment cycle

• Endometrial Thickness

  Cycle day 21-24 of 2nd treatment cycle

Study Arms (2)

Letrozole

ACTIVE COMPARATOR

Letrozole 2.5 mg orally for 5 days on cycle days 3-7 in first study treatment cycle. Participants who ovulate and do not become pregnant will repeat the same treatment protocol for their next study cycle. Participants who do not ovulate will repeat the protocol with Letrozole dose increase of 2.5 mg daily in the next treatment cycle, to a maximum dose of 7.5 mg in the 3rd cycle.

Drug: Letrozole

Letrozole + Clomiphene Citrate

EXPERIMENTAL

Letrozole 2.5 mg orally for 5 days on cycle days 3-7 AND Clomiphene Citrate 50 mg orally for 5 days on cycle days 3-7. Participants who ovulate and do not become pregnant will repeat the same treatment protocol for their next study cycle. Participants who do not ovulate will repeat the protocol with Letrozole dose increase of 2.5mg daily in the next treatment cycle to a maximum dose of 7.5 mg in the 3rd cycle, while maintaining the same dose of Clomiphene Citrate.

Drug: Letrozole; Drug: Clomiphene Citrate

Interventions

Letrozole DRUG

Letrozole tablet

Also known as: femara

Letrozole; Letrozole + Clomiphene Citrate

Clomiphene Citrate DRUG

Clomiphene Citrate tablet

Also known as: Clomid, Clomiphene

Letrozole + Clomiphene Citrate

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64)

You may qualify if:

• Willing to comply with all study procedures and be available for the duration of the study
• Diagnosis of infertility: Inability of couple to achieve successful pregnancy after 12 months of regular time unprotected intercourse in women less than 35 years of age; and after 6 months of regular intercourse without use of contraception in women 35 years and older. Women that have anovulation or oligomenorrhea are also considered to meet diagnosis of infertility, without meeting the time constraints described above.
• Diagnosis of polycystic ovary syndrome based on Revised Rotterdam criteria.
• Ability to have regular intercourse during the ovulation induction phase of the study.
• Partner with a normal sperm concentration of 15 million/mL and with normal motility of \>40% according to World Health Organization cutoff points or greater than 10 million total motile sperm count OR has fathered a pregnancy in the past.

You may not qualify if:

• Current pregnancy
• Current use of hormonal contraception; use of any type of combined contraceptive or oral progestins within the past month; or use of hormonal implants or depo progestins within the past 3 months
• Other known cause of infertility: endometriosis, tubal factor, uterine abnormalities
• Uncorrected thyroid disease
• Untreated hyperprolactinemia
• Medical conditions in which avoiding pregnancy is recommended until under improved control: poorly controlled Type 1 or Type 2 diabetes, poorly controlled hypertension
• Contraindications to clomiphene citrate: hypersensitivity to clomiphene citrate or any of its components, history of liver disease or known liver disease, unknown cause of abnormal uterine bleeding, or intracranial lesion
• Contraindications to letrozole: hypersensitivity to letrozole or any of its components
• Use of medications known to affect reproductive function or metabolism or that are an absolute contraindication during pregnancy within the past month
• If patients are suspected based on clinical findings for other etiologies that mimic PCOS, work up must be completed to exclude other etiologies prior to enrollment (i.e. Cushing's syndrome, androgen-secreting tumor)

Sponsors & Collaborators

• Rachel Mejia: lead
• Society for Reproductive Investigation: collaborator
• American Society for Reproductive Medicine: collaborator
• University of Wisconsin, Madison: collaborator

Study Sites (4)

University of Iowa Hospitals & Clinics - Davenport Clinic

Davenport, Iowa, 52807, United States

Location

University of Iowa Hospitals & Clinics

Iowa City, Iowa, 52242, United States

Location

University of Iowa Hospitals & Clinics- West Des Moines Clinic

West Des Moines, Iowa, 50266, United States

Location

University of Wisconsin

Madison, Wisconsin, 53562, United States

Location

MeSH Terms

Conditions

Polycystic Ovary Syndrome; Infertility

Interventions

Letrozole; Clomiphene

Condition Hierarchy (Ancestors)

Ovarian Cysts; Cysts; Neoplasms; Ovarian Diseases; Adnexal Diseases; Genital Diseases, Female; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Genital Diseases; Gonadal Disorders; Endocrine System Diseases

Intervention Hierarchy (Ancestors)

Nitriles; Organic Chemicals; Triazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Stilbenes; Benzylidene Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons

Results Point of Contact

• Title: Rachel Mejia, DO
• Organization: University of Iowa

rachel-mejia@uiowa.edu

319-356-3143

Study Officials

• Rachel Mejia, DO

  University of Iowa Hospitals & Clinics

  PRINCIPAL INVESTIGATOR

Publication Agreements

• PI is Sponsor Employee: No
• Restrictive Agreement: No

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR INVESTIGATOR
• PI Title: Clinical Assistant Professor

Study Record Dates

• First Submitted: December 28, 2021
• First Posted: January 25, 2022
• Study Start: October 26, 2020
• Primary Completion: April 12, 2024
• Study Completion: December 1, 2025
• Last Updated: April 15, 2025
• Results First Posted: April 15, 2025

Record last verified: 2025-03

Locations

US (4)