Trial Outcomes & Findings for Mineralocorticoid Antagonism and Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney Disease (ADPKD) (NCT NCT01853553)

Results Overview

FMD will be determined using high-resolution ultrasonography

Recruitment status

COMPLETED

Study phase

PHASE3

Target enrollment

61 participants

Primary outcome timeframe

Baseline and 6 months.

Results posted on

2019-08-20

Participant Flow

Eligible participants were enrolled at the University of Colorado Denver Anschutz Medical Campus between July 2014 and June 2016 (the trial concluded according to enrollment determined by power calculations described below).Although Grant was awarded in 2013, recruitment did not start until 2014.

Participants were excluded if they had an average serum potassium \>5.5 mEq/l or any single value \>6.0 mEq/l in the past 6 months, received an aldosterone antagonist in the past 6 months, and were using a potassium sparing diuretic or other medication that could contribute to hyperkalemia.

Participant milestones

Participant milestones
Measure	Spironolactone Active arm Spironolactone Participants were then randomized by the study coordinator according to a computer-generated random allocation sequence and received either the mineralocorticoid antagonist spironolactone or matching placebo. Participants were dosed at 25 mg/day for 4 weeks, with dosing escalated to 50 mg/day for the remainder of the study if tolerated by an individual participant.	Sugar Pill Placebo Sugar pill
Overall Study STARTED	29	32
Overall Study COMPLETED	28	32
Overall Study NOT COMPLETED	1	0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Mineralocorticoid Antagonism and Endothelial Dysfunction in Autosomal Dominant Polycystic Kidney Disease (ADPKD)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Spironolactone n=29 Participants Active arm Spironolactone Participants were then randomized by the study coordinator according to a computer-generated random allocation sequence and received either the mineralocorticoid antagonist spironolactone or matching placebo. Participants were dosed at 25 mg/day for 4 weeks, with dosing escalated to 50 mg/day for the remainder of the study if tolerated by an individual participant.	Sugar Pill n=32 Participants Placebo Sugar pill	Total n=61 Participants Total of all reporting groups
Age, Continuous	34 years STANDARD_DEVIATION 10 • n=5 Participants	34 years STANDARD_DEVIATION 9 • n=7 Participants	34 years STANDARD_DEVIATION 10 • n=5 Participants
Sex: Female, Male Female	13 Participants n=5 Participants	20 Participants n=7 Participants	33 Participants n=5 Participants
Sex: Female, Male Male	16 Participants n=5 Participants	12 Participants n=7 Participants	28 Participants n=5 Participants

PRIMARY outcome

Timeframe: Baseline and 6 months.

FMD will be determined using high-resolution ultrasonography

Outcome measures

Outcome measures
Measure	Spironolactone n=28 Participants Active arm Spironolactone	Sugar Pill n=32 Participants Placebo Sugar pill
Change From Baseline in Flow Mediated Dilation at 6 Months.	-0.2 Percent change. Standard Deviation 3.2	-0.4 Percent change. Standard Deviation 4.7

SECONDARY outcome

Timeframe: Baseline and 6 months

Aortic pulse wave velocity, a measure of large elastic arterial stiffness, and carotid compliance, a measure of large artery distensibility, will be determined. A transcutaneous custom tonometers (Noninvasive Hemodynamics Workstation, Cardiovascular Engineering Inc., Norwood, MA) will be positioned at the aorta and femoral artery to measure pulse wave velocity, and carotid artery compliance (and the β-stiffness index, a more blood pressure independent measure of local arterial stiffness) will be measured non-invasively using simultaneous high-resolution ultrasonography and applanation tonometry). Higher values correspond to greater stiffness.

Outcome measures

Outcome measures
Measure	Spironolactone n=28 Participants Active arm Spironolactone	Sugar Pill n=32 Participants Placebo Sugar pill
Change From Baseline in Vascular Stiffness at 6 Months.	-37 m/s Standard Deviation 78	-1 m/s Standard Deviation 89

OTHER_PRE_SPECIFIED outcome

Timeframe: Baseline and 6 months.

All markers of oxidative stress will be assayed by multiplexed validated liquid chromatography (LC)/ LC-mass spectrometry (MS)/ MS.

Outcome measures

Outcome data not reported

Adverse Events

Spironolactone

Serious events: 0 serious events

Other events: 0 other events

Deaths: 0 deaths

Sugar Pill

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

Dr. Michel Chonchol

University of Colorado

Phone: 303-724-7796

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place