Amiloride for Resistant Hypertension

Phase 4

Completed

• Conditions: Hypertension; Type 2 Diabetes Mellitus; Microalbuminuria
• Interventions: Drug: Amiloride

• Registration Number: NCT02122731
• Lead Sponsor: Ib Abildgaard Jacobsen

Brief Summary

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

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

Study Timeline

• Study Start: 2010-11
• Primary Completion: 2012-07
• Study Completion: 2012-08
• Status Verified: 2014-04
• Study First Submitted: 2014-04-23
• Study First Submitted QC: 2014-04-23
• Last Update Submitted: 2014-04-23
• Study First Posted: 2014-04-24
• Last Update Posted: 2014-04-24

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 80

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: SINGLE_GROUP

Arm && Interventions

Group	Intervention	Description
Amiloride	Amiloride	This is a non-randomized and non-controlled study with only one treatment arm with amiloride.

Primary Outcome Measures

Name	Time	Method
average daytime systolic and diastolic blood pressure	8 weeks	ambulatory blood pressure monitoring was performed at baseline and after 8 weeks intervention with amiloride

Secondary Outcome Measures

Name	Time	Method
plasma potassium	after 4 and 8 weeks	plasma potassium tend to increase during amiloride treatment
urine plasminogen and plasmin	at baseline and after 8 weeks of amiloride treatment	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.
Urinary albumin excretion	after 8 weeks	Urine albumin was measured at baseline and after 8 weeks of amiloride treatment.
urinary urokinase plasminogen activator (uPA) activity	At baseline and after 8 weeks of amiloride treatment	uPA exist in urine where it cleaves plasminogen to plasmin. uPA is possible secreted fra the tubulus cells

Trial Locations

Locations (4)

Sydvestjysk Hospital, Esbjerg; 🇩🇰 Esbjerg, Denmark

Sygehus Lillebaelt.; 🇩🇰 Fredericia, Denmark

Steno Diabetes Center; 🇩🇰 Gentofte, Denmark

Odense University Hospital, Department of Endocrinology; 🇩🇰 Odense, Denmark