Trial Outcomes & Findings for Effect of Estradiol+Drospirenone Versus Estradiol+MPA on Endothelial Function (NCT NCT01109979)

Last Updated: 2016-07-12

Results Overview

This crossover study examined the effects of E+MPA versus E+DRSP on brachial artery reactivity (BAR) assessed after six weeks of treatment. BAR is a noninvasive measure of endothelium-dependent flow-mediated vasodilation (FMD) of the brachial artery. With this technique, inflation of an arm blood pressure cuff to suprasystolic blood pressure causes relative ischemia downstream to the cuff. Upon deflation, a brief state of increased blood flow occurs (reactive hyperemia), and the resulting increase in shear stress causes nitric oxide release and resulting vasodilation of the brachial artery (flow-mediated vasodilation). The flow-mediated changes in brachial artery diameter can be imaged by ultrasound and measured as an index of peripheral vasomotor function. BAR correlates with invasive assessments of coronary endothelial function as well as multiple cardiovascular risk factors.

Recruitment status

COMPLETED

Study phase

PHASE4

Target enrollment

24 participants

Primary outcome timeframe

%FMD after 6 weeks of treatment

Results posted on

2016-07-12

Participant Flow

Postmenopausal women ages 45 and 75 were recruited 2009- 2011 via flyers, newspaper advertisements, Craigslist, RSVP for Health, and websites.

Subjects were excluded after screening procedures due to history of hypertension, cardiovascular disease, hyperlipidemia, diabetes, liver disease, cancer, elevated creatinine/potassium levels, abnormal thyroid function, and evidence that menopause was not completed.

Participant milestones

Participant milestones
Measure	E+MPA, Then E+DRSP Estradiol (E) 1 mg orally per day + medroxyprogesterone acetate (MPA) 2.5 mg orally per day for 6 weeks, then 4 week washout before Estradiol (E) 1 mg orally per day + Drospirenone (DRSP) 0.5 mg orally per day for 6 weeks	E+DRSP, Then E+MPA Estradiol (E) 1 mg orally per day + Drospirenone (DRSP) 0.5 mg orally per day for 6 weeks, then 4 week washout before Estradiol (E) 1 mg orally per day + medroxyprogesterone acetate (MPA) 2.5 mg orally per day for 6 weeks
Overall Study STARTED	12	12
Overall Study COMPLETED	10	11
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Reasons for withdrawal
Measure	E+MPA, Then E+DRSP Estradiol (E) 1 mg orally per day + medroxyprogesterone acetate (MPA) 2.5 mg orally per day for 6 weeks, then 4 week washout before Estradiol (E) 1 mg orally per day + Drospirenone (DRSP) 0.5 mg orally per day for 6 weeks	E+DRSP, Then E+MPA Estradiol (E) 1 mg orally per day + Drospirenone (DRSP) 0.5 mg orally per day for 6 weeks, then 4 week washout before Estradiol (E) 1 mg orally per day + medroxyprogesterone acetate (MPA) 2.5 mg orally per day for 6 weeks
Overall Study Physician Decision	2	0
Overall Study Withdrawal by Subject	0	1

Baseline Characteristics

Effect of Estradiol+Drospirenone Versus Estradiol+MPA on Endothelial Function

Baseline characteristics by cohort

PRIMARY outcome

Timeframe: %FMD after 6 weeks of treatment

Population: The number of participants for analysis includes only the participants that completed a baseline assessment and at least one of the treatment arms.

Outcome measures

Outcome measures
Measure	E+MPA n=21 Participants Estradiol (E) 1 mg orally per day + medroxyprogesterone acetate (MPA) 2.5 mg orally per day for 6 weeks	E+DRSP n=21 Participants Estradiol (E) 1 mg orally per day + Drospirenone (DRSP) 0.5 mg orally per day for 6 weeks
Brachial Artery Reactivity % Flow Mediated Dilation (BAR %FMD)	5.49 % FMD after 6 weeks of treatment Standard Deviation 3.32	3.39 % FMD after 6 weeks of treatment Standard Deviation 3.18

Adverse Events

E+MPA

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

E+DRSP

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

Ellen Seely, MD

Brigham and Women's Hospital

Phone: 617-732-5012

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	E+MPA, Then E+DRSP n=12 Participants Estradiol (E) 1 mg orally per day + medroxyprogesterone acetate (MPA) 2.5 mg orally per day for 6 weeks, then 4 week washout before Estradiol (E) 1 mg orally per day + Drospirenone (DRSP) 0.5 mg orally per day for 6 weeks	E+DRSP, Then E+MPA n=12 Participants Estradiol (E) 1 mg orally per day + Drospirenone (DRSP) 0.5 mg orally per day for 6 weeks, then 4 week washout before Estradiol (E) 1 mg orally per day + medroxyprogesterone acetate (MPA) 2.5 mg orally per day for 6 weeks	Total n=24 Participants Total of all reporting groups
Age, Categorical <=18 years	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Age, Categorical Between 18 and 65 years	8 Participants n=5 Participants	10 Participants n=7 Participants	18 Participants n=5 Participants
Age, Categorical >=65 years	4 Participants n=5 Participants	2 Participants n=7 Participants	6 Participants n=5 Participants
Sex: Female, Male Female	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Hispanic or Latino	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Ethnicity (NIH/OMB) Not Hispanic or Latino	12 Participants n=5 Participants	12 Participants n=7 Participants	24 Participants n=5 Participants
Ethnicity (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	1 Participants n=7 Participants	1 Participants n=5 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Black or African American	1 Participants n=5 Participants	1 Participants n=7 Participants	2 Participants n=5 Participants
Race (NIH/OMB) White	11 Participants n=5 Participants	10 Participants n=7 Participants	21 Participants n=5 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants