Amiloride for Resistant Hypertension

Study Overview
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Brief Summary
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To evaluate the antihypertensive effect of amiloride added to triple antihypertensive therapy in patients with resistant hypertension (RH) and type 2 diabetes mellitus (T2DM)

Detailed Description
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The primary objective of this study was to evaluate the antihypertensive effect of amiloride added to triple antihypertensive treatment in patients with resistant hypertension and type 2 diabetes mellitus in an open-labelled, non- controlled and non-randomized interventional study. The secondary objectives were to evaluate the additional effects of amiloride on: Urinary albumin excretion Blood pressure control, how many patients reached blood pressure control when amiloride was added to previous triple antihypertensive treatment. Plasminogen and plasmin excretion (ENaC activity) in the micro-and macroalbuminuric patients in the cohort. Urokinase plasminogen activator (uPA) activity

Official Title
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Southern Danish Hypertension and Diabetes Study (SDHDS) With Amiloride

Conditions
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Hypertension, Type 2 Diabetes Mellitus, Microalbuminuria

Intervention / Treatment
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* Drug: Amiloride


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: diagnosed with resistant hypertension (average daytime BP >130and/or >80 mmHg by ambulatory monitoring in spite of treatment with 3 antihypertensive drugs including a diuretic and an angiotensin coverting enzyme inhibitor (AECi) or angiotensin recpetor blocker (ARBs) and a third optional, all in optimal dosages. type 2 diabetes prior participant in a randomized controlled trial with spironolactone, but after a wash-out periods of minimum two weeks (NCT01062763) Exclusion Criteria: Office blood pressure (BP) >180/110 mmHg daytime average BP by ambulatory monitoring > 170/85 mmHg heart failure (NYHA III-IV) Cardiac arrythmia HbA1C > 10% severe dyslipidemia known or with signs of secondary hypertension estimated glomerular filtration rate (eGFR) <50ml/min per 1.73 m2 prior intolerance to spironolactone or amiloride fertility without oral contraception pregnancy lactation

Ages Eligible for Study
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Minimum Age: 30 Years
Maximum Age: 75 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Amiloride<br>This is a non-randomized and non-controlled study with only one treatment arm with amiloride. | Drug: Amiloride<br>* 5 mg(daily of amiloride was added to patients triple antihypertensive therapy and increased to 10 mg/daily if office blood pressure at 4 weeks was above 130/80 mmHg.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| average daytime systolic and diastolic blood pressure | ambulatory blood pressure monitoring was performed at baseline and after 8 weeks intervention with amiloride | 8 weeks | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Urinary albumin excretion | Urine albumin was measured at baseline and after 8 weeks of amiloride treatment. | after 8 weeks | 
| plasma potassium | plasma potassium tend to increase during amiloride treatment | after 4 and 8 weeks | 
| urinary urokinase plasminogen activator (uPA) activity | uPA exist in urine where it cleaves plasminogen to plasmin. uPA is possible secreted fra the tubulus cells | At baseline and after 8 weeks of amiloride treatment | 
| urine plasminogen and plasmin | U-plasminogen is filtered to urine in patients with microalbuminuria. In urine plasminogen is activated to plasmin by urokinase plasminogen activator.Plasmin activates the epithelial sodium channel. | at baseline and after 8 weeks of amiloride treatment | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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antihypertensive therapy, amiloride, add-on, resistant hypertension, blood pressure control, type 2 diabetes mellitus,, microalbuminuria.