Hormone Replacement Therapy for Use in Postmenopausal Women for Relief of Hot Flushes and Urogenital Symptoms.

A Multicenter, Double-Blind, Controlled, Randomized Study to Compare the Efficacy in Relief of Hot Flushes in Women Receiving Oral Estradiol Acetate Tablets, Oral Estradiol Tablets or Oral Conjugated Equine Estrogens

Status

Completed

Phases

Phase 3

Study type

Interventional

Source

ClinicalTrials.gov

Registry ID

NCT01070979

Enrollment

249

Registered

2010-02-18

Start date

2003-02-28

Completion date

2003-09-30

Last updated

2013-04-22

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Hormone Replacement Therapy

Brief summary

Multicenter, double-blind, controlled, parallel group, randomized study to compare the clinical benefit of Estradiol acetate tablets, estradiol tablets and conjugated equine estrogen tablets, each administered orally, once daily, to postmenopausal women.

Interventions

DRUGEstradiol acetate

Tablet containing 0.9 mg E3A, daily oral administration.

DRUGEstradiol

Tablet containing 1 mg estradiol, daily oral administration.

DRUGConjugated equine estrogens

Tablet containing 0.625 mg CEE, daily oral administration.

Study design

Allocation

RANDOMIZED

Intervention model

PARALLEL

Primary purpose

TREATMENT

Masking

QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)

Eligibility

Sex/Gender

FEMALE

Age

35 Years to No maximum

Healthy volunteers

Inclusion criteria

1. Age ≥ 40 years of age; bilateral oophorectomy ≥ 35 years of age. 2. Non-hysterectomized women: * Amenorrhea for ≥ 12 months or * Amenorrhea for ≤ 12 months, but longer than 6 months, and serum FSH (follicle stimulating hormone) levels \> 40 units/L and serum estradiol levels \< 20 pg /mL, Hysterectomized women: * Bilateral oophorectomy - subjects may enter the study 6 weeks after surgery or * History of removal of ovaries may be confirmed by - serum FSH levels \> 40 units/L and serum estradiol levels \< 20 pg/mL or via surgical report / ultrasound. 3. Seven or more moderate or severe hot flushes daily for 1 week or 60 or more moderate or severe flushes in 1 week during the 2 week screening period prior to study entry.

Exclusion criteria

1. Hormone therapy administered via the following routes and during the specified timeframes: oral within 8 weeks, vaginal (rings, creams, gels) within 1 week, transdermal within 4 weeks, intramuscular within 6 weeks, progestational implants, estrogen or estrogen/progestational injectable drug therapy within 3 months, estrogen pellet or progestational injectable within 6 months. 2. Abnormal Pap smear suggestive of low grade squamous intraepithelial lesion (LGSIL) or worse. Enrollment of subjects with an ASCUS (atypical squamous cells of undetermined significance) interpretation must be discussed with the sponsor prior to randomization. 3. Urinary tract infection 4. Congestive heart failure 5. Uncontrolled hypertension; sitting systolic BP ≥ 160 mmHg or diastolic ≥ 95 mmHg 6. History of stroke or transient ischemic attacks 7. Treatment with anticoagulants (heparin or warfarin). 8. Uncontrolled thyroid disorders. 9. Insulin-dependent diabetes mellitus. 10. Increase frequency or severity of headaches including migraines during previous estrogen therapy.

Design outcomes

Primary

Measure	Time frame	Description
Mean Change From Baseline in the Number of Moderate to Severe Hot Flushes, Week 4, ITT (Intention to Treat) Population	Baseline to Week 4	Severity of hot flush definitions: mild - sensation of heat without perspiration, moderate - sensation of heat with perspiration, able to continue activity, severe - sensation of heat with perspiration, causing the subject to stop activity or awaken from sleep
Mean Change From Baseline in the Number of Moderate to Severe Hot Flushes, Week 12, ITT Population	Baseline to Week 12	Severity of hot flush definitions: mild - sensation of heat without perspiration, moderate - sensation of heat with perspiration, able to continue activity, severe - sensation of heat with perspiration, causing the subject to stop activity or awaken from sleep

Secondary

Measure	Time frame	Description
Mean Change From Baseline in Total Urogenital Symptom Score, Week 4, ITT Population	Baseline to Week 4	Urogenital Symptom Severity scored none=0, mild=1, moderate=2, severe=3.
Mean Change From Baseline in the Severity of Moderate to Severe Hot Flushes, Week 4, ITT Population	Baseline to Week 4	Patient self-reported outcome. Severity of hot flush definitions: mild (1) - sensation of heat without perspiration, moderate (2) - sensation of heat with perspiration, able to continue activity, severe (3) - sensation of heat with perspiration, causing the subject to stop activity or awaken from sleep. Minimum 0/no hot flushes, Maximum 3/all severe hot flushes. Lower the score the greater the improvement in reducing hot flushes.
Change From Baseline in Total Urogenital Symptom Score, Week 12, ITT Population	Baseline to Week 12	Urogenital Symptom Severity scored none=0, mild=1, moderate=2, severe=3.
Change From Baseline in Total Urogenital Symptom Score, Week 8, ITT Population	Baseline to Week 8	Urogenital Symptom Severity scored none=0, mild=1, moderate=2, severe=3.
Mean Change From Baseline in the Severity of Moderate to Severe Hot Flushes, Week 12, ITT Population	Baseline to Week 12	Patient self-reported outcome. Severity of hot flush definitions: mild (1) - sensation of heat without perspiration, moderate (2) - sensation of heat with perspiration, able to continue activity, severe (3) - sensation of heat with perspiration, causing the subject to stop activity or awaken from sleep. Minimum 0/no hot flushes, Maximum 3/all severe hot flushes. Lower the score the greater the improvement in reducing hot flushes.

Countries

United States

Participant flow

Recruitment details

Enrollment of postmenopausal women for relief of hot flushes and urogenital symptoms beginning Feb '03 at 33 sites in the US.

Pre-assignment details

Discontinue estrogen/hormone therapy prior to enrollment

Participants by arm

Arm	Count
Estradiol Acetate (E3A) 1 tablet daily containing 0.9 mg estradiol acetate	79
Estradiol 1 tablet daily containing 1 mg estradiol	85
Conjugated Equine Estrogens (CEE) 1 tablet daily containing 0.625 mg conjugated equine estrogen	85
Total	249

Withdrawals & dropouts

Period	Reason	FG000	FG001	FG002
Overall Study	Adverse Event	2	3	3
Overall Study	Lost to Follow-up	2	1	1
Overall Study	No study drug taken	0	1	0
Overall Study	Protocol Violation	0	2	6
Overall Study	Surgery, moving, personal, abn. labs	4	4	2
Overall Study	Withdrawal by Subject	3	1	1

Baseline characteristics

Characteristic	Estradiol Acetate (E3A)	Estradiol	Conjugated Equine Estrogens (CEE)	Total
Age Continuous	52.2 years STANDARD_DEVIATION 6.6	52.3 years STANDARD_DEVIATION 7	53.8 years STANDARD_DEVIATION 6.3	52.8 years STANDARD_DEVIATION 6.7
Region of Enrollment United States	79 participants	85 participants	85 participants	249 participants
Sex: Female, Male Female	79 Participants	85 Participants	85 Participants	249 Participants
Sex: Female, Male Male	0 Participants	0 Participants	0 Participants	0 Participants

Adverse events

Event type	EG000 affected / at risk	EG001 affected / at risk	EG002 affected / at risk
deaths Total, all-cause mortality	— / —	— / —	— / —
other Total, other adverse events	19 / 79	25 / 84	30 / 85
serious Total, serious adverse events	0 / 79	1 / 84	0 / 85

Outcome results

Primary

Mean Change From Baseline in the Number of Moderate to Severe Hot Flushes, Week 12, ITT Population

Severity of hot flush definitions: mild - sensation of heat without perspiration, moderate - sensation of heat with perspiration, able to continue activity, severe - sensation of heat with perspiration, causing the subject to stop activity or awaken from sleep

Time frame: Baseline to Week 12