Arterial Hypertension, Diabetes Mellitus, Hypertension, Resistant to Conventional Therapy
Conditions
Keywords
hypertension, spironolactone, antihypertensive treatment, Type-2 diabetes
Brief summary
The purpose of this study is to estimate the effect of spironolactone on blood pressure resistant to therapy in type-2 diabetics.
Detailed description
The primary object of the study is to estimate the effect of addition of low dose spironolactone to antihypertensive treatment with at least three antihypertensive drugs in patients with type-2 diabetes and blood pressure over 130/80 mmHg. Secondary aims are to estimate how many of these patients have their blood pressure controlled by the addition of spironolactone, to investigate whether the addition of spironolactone affects insulin sensitivity and urinary protein secretion and to estimate the incidence of adverse effects of the aldosterone antagonist.
Interventions
DRUGspironolactone
25 to 50 mg once daily
DRUGplacebo
addition of placebo 1 to 2 tablets daily
Sponsors
Ib Abildgaard Jacobsen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age \< 75 years * Type-2 diabetes * Therapy resistant hypertension (by ABPM) * Treatment with at least 3 antihypertensives
Exclusion criteria
* HbA1c \> 10.0 * BP \> 180/110 mmHg * Secondary hypertension * Intolerance to spironolactone * Permanent treatment with nonsteroidal antiinflammatory drugs or systemic glucocorticoids * Total cholesterol 10 mmol/l * New York Heart Association class III and IV * Pregnancy or planned pregnancy * Psychiatric disease * Malignant disease * Insufficient adherence
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Change of of Systolic Blood Pressure | 4 months | Change of systolic blood pressure from baseline to study end at four months. |
| Change of Diastolic Blood Pressure | 4 months | Change of diastolic blood pressure from baseline to study end at four months. |
Secondary
| Measure | Time frame |
|---|---|
| Adverse Effects | 4 months |
Participant flow
Recruitment details
Patients recruited from outpatient clinics of endocrinology at two university hospitals and two general hospitals in the period from May 2010 to March 2012.
Pre-assignment details
163 patints screened. 44 screenfailures due to exclusion criteria as indicated. 119 randomized
Participants by arm
| Arm | Count |
|---|---|
| Addition of Spironolactone spironolactone is added to previous antihypertensive treatment
placebo : addition of placebo 1 to 2 tablets daily
spironolactone : 25 to 50 mg once daily | 61 |
| Placebo | 58 |
| Total | 119 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | Adverse Event | 3 | 4 |
Baseline characteristics
| Characteristic | Placebo | Addition of Spironolactone | Total |
|---|---|---|---|
| Age, Categorical <=18 years | 0 Participants | 0 Participants | 0 Participants |
| Age, Categorical >=65 years | 30 Participants | 27 Participants | 57 Participants |
| Age, Categorical Between 18 and 65 years | 28 Participants | 34 Participants | 62 Participants |
| Age, Continuous | 63.9 years STANDARD_DEVIATION 6.9 | 62.9 years STANDARD_DEVIATION 7.1 | 63.4 years STANDARD_DEVIATION 6.9 |
| Region of Enrollment Denmark | 58 participants | 61 participants | 119 participants |
| Sex: Female, Male Female | 13 Participants | 15 Participants | 28 Participants |
| Sex: Female, Male Male | 45 Participants | 46 Participants | 91 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 61 | 0 / 58 |
| serious Total, serious adverse events | 1 / 61 | 0 / 58 |
Outcome results
Primary
Change of Diastolic Blood Pressure
Change of diastolic blood pressure from baseline to study end at four months.
Time frame: 4 months
Population: Analyzed by intention to treat and last observation carried forward
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Addition of Spironolactone | Change of Diastolic Blood Pressure | -3.9 mm Hg |
| Placebo | Change of Diastolic Blood Pressure | -0.3 mm Hg |
Primary
Change of of Systolic Blood Pressure
Change of systolic blood pressure from baseline to study end at four months.
Time frame: 4 months
Population: Analysis by intention to treat using LOCF
| Arm | Measure | Value (MEAN) |
|---|---|---|
| Addition of Spironolactone | Change of of Systolic Blood Pressure | -9.6 mm Hg |
| Placebo | Change of of Systolic Blood Pressure | -0.7 mm Hg |
Secondary
Adverse Effects
Time frame: 4 months
Population: Intention to treat
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Addition of Spironolactone | Adverse Effects | 4 participants |
| Placebo | Adverse Effects | 0 participants |