Trial Outcomes & Findings for Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease (NCT NCT00865124)

Last Updated: 2017-06-14

Results Overview

Coronary flow reserve (CFR), or myocardial perfusion reserve, was assessed via cardiac positron emission tomography (PET). CFR is the ratio of adenosine-stimulated blood flow through myocardium to resting blood flow through myocardium. An improvement in coronary flow reserve is beneficial.

Recruitment status

COMPLETED

Study phase

Target enrollment

69 participants

Primary outcome timeframe

Baseline and six months

Results posted on

2017-06-14

Participant Flow

Participant milestones

Participant milestones
Measure	Spironolactone (MR Blockade) 25 mg capsule daily for 6 months	Hydrochlorothiazide + Potassium Hydrochlorothiazide (HCTZ) + potassium, 12.5 mg/10 milliequivalents (mEq) capsule daily	Placebo Placebo capsule daily
Overall Study STARTED	27	25	17
Overall Study COMPLETED	23	24	17
Overall Study NOT COMPLETED	4	1	0

Reasons for withdrawal

Reasons for withdrawal
Measure	Spironolactone (MR Blockade) 25 mg capsule daily for 6 months	Hydrochlorothiazide + Potassium Hydrochlorothiazide (HCTZ) + potassium, 12.5 mg/10 milliequivalents (mEq) capsule daily	Placebo Placebo capsule daily
Overall Study Physician Decision	2	1	0
Overall Study Withdrawn consent	2	0	0

Baseline Characteristics

Role of Mineralocorticoid Receptor in Diabetic Cardiovascular Disease

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Spironolactone (MR Blockade) n=23 Participants Spironolactone: 25 mg capsule daily for 6 months	Hydrochlorothiazide + Potassium n=24 Participants Hydrochlorothiazide + potassium: hydrochlorothiazide (HCTZ) + potassium, 12.5 mg/10 mEq capsule daily	Placebo Capsule n=17 Participants Placebo: Placebo capsule daily	Total n=64 Participants Total of all reporting groups
Age, Continuous	56 years STANDARD_DEVIATION 6 • n=99 Participants	53 years STANDARD_DEVIATION 7 • n=107 Participants	55 years STANDARD_DEVIATION 10 • n=206 Participants	54.72 years STANDARD_DEVIATION 7.66 • n=7 Participants
Sex: Female, Male Female	6 Participants n=99 Participants	11 Participants n=107 Participants	7 Participants n=206 Participants	24 Participants n=7 Participants
Sex: Female, Male Male	17 Participants n=99 Participants	13 Participants n=107 Participants	10 Participants n=206 Participants	40 Participants n=7 Participants

PRIMARY outcome

Timeframe: Baseline and six months

Population: All participants with data available for this outcome measure.

Outcome measures

Outcome measures
Measure	Spironolactone (MR Blockade) n=22 Participants 25 mg capsule daily for 6 months	Hydrochlorothiazide + Potassium n=22 Participants Hydrochlorothiazide (HCTZ) + potassium, 12.5 mg/10 mEq capsule daily	Placebo n=16 Participants Placebo capsule daily
Change in Coronary Flow Reserve From Baseline to 6 Months	0.33 ratio Standard Deviation 0.83	-0.10 ratio Standard Deviation 0.65	0.02 ratio Standard Deviation 1.03

SECONDARY outcome

Timeframe: Baseline and six months

Population: All participants with data available for this outcome measure.

Diastolic function was assessed via tissue doppler imaging (TDI) by echocardiography to determine left ventricular diastolic function before and after 6 months of treatment.

Outcome measures

Outcome measures
Measure	Spironolactone (MR Blockade) n=23 Participants 25 mg capsule daily for 6 months	Hydrochlorothiazide + Potassium n=24 Participants Hydrochlorothiazide (HCTZ) + potassium, 12.5 mg/10 mEq capsule daily	Placebo n=17 Participants Placebo capsule daily
Change in Mitral Annulus Velocities on Tissue Doppler (Delta E/e' Ratio), a Measure of Diastolic Function	0.02 ratio Standard Deviation 1.61	0.06 ratio Standard Deviation 1.35	0.64 ratio Standard Deviation 1.95

SECONDARY outcome

Timeframe: Baseline and six months

Population: All participants with data available for this outcome measure at the given time-point.

Diastolic function was assessed via tissue doppler imaging (TDI) by echocardiography to determine left ventricular diastolic function before and after 6 months of treatment; and in response to acute administration (3 nanograms/kg/min for 60 min) of the vasoactive agent, Angiotensin II.

Outcome measures

Outcome measures
Measure	Spironolactone (MR Blockade) n=27 Participants 25 mg capsule daily for 6 months	Hydrochlorothiazide + Potassium n=25 Participants Hydrochlorothiazide (HCTZ) + potassium, 12.5 mg/10 mEq capsule daily	Placebo n=17 Participants Placebo capsule daily
Mitral Annulus Velocities on Tissue Doppler (Delta E/e' Ratio), a Measure of Diastolic Function (With Angiotensin II) Pre-treatment, E/e', baseline	6.67 ratio Standard Deviation 1.93	6.72 ratio Standard Deviation 1.93	6.55 ratio Standard Deviation 2.24
Mitral Annulus Velocities on Tissue Doppler (Delta E/e' Ratio), a Measure of Diastolic Function (With Angiotensin II) Pre-treatment, E/e', Post-ANGII	7.09 ratio Standard Deviation 1.96	7.06 ratio Standard Deviation 1.66	6.70 ratio Standard Deviation 3.08
Mitral Annulus Velocities on Tissue Doppler (Delta E/e' Ratio), a Measure of Diastolic Function (With Angiotensin II) 6 months post-treatment, E/e', baseline	6.76 ratio Standard Deviation 1.57	7.03 ratio Standard Deviation 1.83	7.35 ratio Standard Deviation 2.26
Mitral Annulus Velocities on Tissue Doppler (Delta E/e' Ratio), a Measure of Diastolic Function (With Angiotensin II) 6 months post-treatment, E/e', Post-ANGII	6.28 ratio Standard Deviation 2.53	5.83 ratio Standard Deviation 2.82	7.48 ratio Standard Deviation 1.59

SECONDARY outcome

Timeframe: Baseline and six months

Population: All participants with data available for this outcome measure at the given time-point.

Renal vasculature was assessed by examining renal plasma flow, or para-aminohippurate (PAH) clearance, basally and in response to acute administration (3 nanograms/kg/min for 60 min) of the vasoactive agent, Angiotensin II.

Outcome measures

Outcome measures
Measure	Spironolactone (MR Blockade) n=27 Participants 25 mg capsule daily for 6 months	Hydrochlorothiazide + Potassium n=25 Participants Hydrochlorothiazide (HCTZ) + potassium, 12.5 mg/10 mEq capsule daily	Placebo n=17 Participants Placebo capsule daily
Change in Renal Plasma Flow Pre-treatment, PAH clearance, baseline	527 mL/min/1.73m^2 Standard Deviation 76	508 mL/min/1.73m^2 Standard Deviation 82	518 mL/min/1.73m^2 Standard Deviation 108
Change in Renal Plasma Flow Pre-treatment, PAH clearance, Post-ANGII	442 mL/min/1.73m^2 Standard Deviation 75	417 mL/min/1.73m^2 Standard Deviation 49	436 mL/min/1.73m^2 Standard Deviation 97
Change in Renal Plasma Flow 6 months post-treatment, PAH clearance, baseline	518 mL/min/1.73m^2 Standard Deviation 97	500 mL/min/1.73m^2 Standard Deviation 80	491 mL/min/1.73m^2 Standard Deviation 87
Change in Renal Plasma Flow 6 months post-treatment, PAH clearance, Post-ANGII	423 mL/min/1.73m^2 Standard Deviation 89	415 mL/min/1.73m^2 Standard Deviation 61	427 mL/min/1.73m^2 Standard Deviation 99

Adverse Events

Spironolactone (MR Blockade)

Serious events: 2 serious events

Other events: 6 other events

Deaths: 0 deaths

Hydrochlorothiazide + Potassium

Serious events: 0 serious events

Other events: 5 other events

Deaths: 0 deaths

Placebo

Serious events: 0 serious events

Other events: 3 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Spironolactone (MR Blockade) n=27 participants at risk 25 mg capsule daily for 6 months	Hydrochlorothiazide + Potassium n=25 participants at risk Hydrochlorothiazide (HCTZ) + potassium, 12.5 mg/10 mEq capsule daily	Placebo n=17 participants at risk Placebo capsule daily
Vascular disorders Pulmonary embolism	3.7% 1/27 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/25 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/17 • 6 months Adverse events are reported for participants who received study treatment.
Investigations Increased potassium	3.7% 1/27 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/25 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/17 • 6 months Adverse events are reported for participants who received study treatment.

Other adverse events

Additional Information

Gail K. Adler

Brigham and Women's Hospital

Phone: 617-732-5661

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Measure	Spironolactone (MR Blockade) n=27 participants at risk 25 mg capsule daily for 6 months	Hydrochlorothiazide + Potassium n=25 participants at risk Hydrochlorothiazide (HCTZ) + potassium, 12.5 mg/10 mEq capsule daily	Placebo n=17 participants at risk Placebo capsule daily
Gastrointestinal disorders Vomiting	0.00% 0/27 • 6 months Adverse events are reported for participants who received study treatment.	4.0% 1/25 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/17 • 6 months Adverse events are reported for participants who received study treatment.
Cardiac disorders Reversible ischemia	3.7% 1/27 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/25 • 6 months Adverse events are reported for participants who received study treatment.	11.8% 2/17 • 6 months Adverse events are reported for participants who received study treatment.
Metabolism and nutrition disorders Hyperglycemia	0.00% 0/27 • 6 months Adverse events are reported for participants who received study treatment.	4.0% 1/25 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/17 • 6 months Adverse events are reported for participants who received study treatment.
Skin and subcutaneous tissue disorders Rash	0.00% 0/27 • 6 months Adverse events are reported for participants who received study treatment.	4.0% 1/25 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/17 • 6 months Adverse events are reported for participants who received study treatment.
Injury, poisoning and procedural complications Injection site reaction	3.7% 1/27 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/25 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/17 • 6 months Adverse events are reported for participants who received study treatment.
Vascular disorders Dilated pulmonary artery	3.7% 1/27 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/25 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/17 • 6 months Adverse events are reported for participants who received study treatment.
Nervous system disorders Dizziness	0.00% 0/27 • 6 months Adverse events are reported for participants who received study treatment.	4.0% 1/25 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/17 • 6 months Adverse events are reported for participants who received study treatment.
Gastrointestinal disorders Nausea	0.00% 0/27 • 6 months Adverse events are reported for participants who received study treatment.	4.0% 1/25 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/17 • 6 months Adverse events are reported for participants who received study treatment.
Gastrointestinal disorders Stomach pain	0.00% 0/27 • 6 months Adverse events are reported for participants who received study treatment.	4.0% 1/25 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/17 • 6 months Adverse events are reported for participants who received study treatment.
Respiratory, thoracic and mediastinal disorders Lung nodule	7.4% 2/27 • 6 months Adverse events are reported for participants who received study treatment.	4.0% 1/25 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/17 • 6 months Adverse events are reported for participants who received study treatment.
Renal and urinary disorders Renal cyst	0.00% 0/27 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/25 • 6 months Adverse events are reported for participants who received study treatment.	5.9% 1/17 • 6 months Adverse events are reported for participants who received study treatment.
Hepatobiliary disorders Liver lesion	0.00% 0/27 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/25 • 6 months Adverse events are reported for participants who received study treatment.	5.9% 1/17 • 6 months Adverse events are reported for participants who received study treatment.
Musculoskeletal and connective tissue disorders Thoracic vertebral hemangioma	0.00% 0/27 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/25 • 6 months Adverse events are reported for participants who received study treatment.	5.9% 1/17 • 6 months Adverse events are reported for participants who received study treatment.
Respiratory, thoracic and mediastinal disorders Nodular opacity in the lung	3.7% 1/27 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/25 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/17 • 6 months Adverse events are reported for participants who received study treatment.
Cardiac disorders Pericardial effusion	3.7% 1/27 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/25 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/17 • 6 months Adverse events are reported for participants who received study treatment.
Cardiac disorders Stress-induced ischemia	0.00% 0/27 • 6 months Adverse events are reported for participants who received study treatment.	8.0% 2/25 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/17 • 6 months Adverse events are reported for participants who received study treatment.
Musculoskeletal and connective tissue disorders Vertebral degeneration	3.7% 1/27 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/25 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/17 • 6 months Adverse events are reported for participants who received study treatment.
Cardiac disorders Atrial septal aneurysm	3.7% 1/27 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/25 • 6 months Adverse events are reported for participants who received study treatment.	0.00% 0/17 • 6 months Adverse events are reported for participants who received study treatment.