Effect of Aliskiren and Hydrochlorothiazide on Kidney Oxygenation in Patients With Hypertension

Effect of Aliskiren 300mg and Hydrochlorothiazide 25mg on Kidney Oxygenation in Patients With Stage 1 and 2 Hypertension: a BOLD-MRI Study

The goal of this project is to evaluate the chronic effect (8 weeks) of RASILEZ 300mg (aliskiren) on renal tissue oxygenation in patients with stage 1-2 hypertension, and to compare the chronic effect (8 weeks) of RASILEZ 300mg (aliskiren) on renal tissue oxygenation in patients with stage 1-2 hypertension with these effects with those of ESIDREX 25mg (hydrochlorothiazide).

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Drug: Aliskiren; Drug: Hydrochlorothiazide

Detailed Description

36 patients with arterial hypertension stage 1-2 (blood pressure: 140/90 and 180/110 mm Hg) will be included in this study and randomized to two groups of 18 patients each: one group will receive RASILEZ 300mg (aliskiren) and one group ESIDREX 25mg (hydrochlorothiazide).

After a two week washout of antihypertensive drugs, baseline and the chronic effect (8 week study drug) of each group will be studied with precise renal hemodynamic measurements (inulin clearance, PAH renal plasma and blood flow, sodium and endogenous lithium excretion, plasma renin, plasma aldosterone, urinary sodium and potassium) and assessment of renal oxygenation with BOLD-MRI (blood oxygen level detection - magnetic resonance imaging).

Drug therapy will be started with an initial 2 weeks on Rasilez 150 mg or HCTZ 12.5 mg followed by a titration to 300 mg Rasilez and 25 mg HCTZ if the treatment is well tolerated. In both groups: a first baseline measurements will be performed before initiating therapy and a second after 8 weeks of treatment (24h after last drug intake) to assess the chronic effect.

Patients already on treatment with antihypertensive drugs can be included in this study, but will undergo a 'wash-out' period of two weeks. After obtaining informed consent, baseline physical examination and office blood pressure measurement will be performed. Office blood pressure will be measured according to the guidelines of the European Society on Hypertension and European Society of Cardiology (ESH-ESC practice guidelines) by an experienced physician. Moreover, patients will measure their home blood pressure twice daily: after 5 minutes of sitting quietly, three measures spaced by 1-2 minutes will be taken in the morning and in the evening. For this purpose, an Omron 705 IT device will be provided to the participants; this device has been widely tested in clinical practice and has been validated for use in clinical studies (12).

Throughout the study, the participants will continue his/her regular diet. The goal should be to keep the salt intake as stable as possible during the study, since salt intake alters the R2* signal. Salt intake will be verified each time before BOLD-MRI measurement by a 24h urine collection (dosing volume, creatinine- and sodium-concentration).

To complete the study we decid to test the acute effect of aliskiren 300mg and Esidrex (hydrochlorthiazide) 25mg in 6 healthy volunteers. We will measure the cortical and medullary R2* signal before drug intake and 3 hours after drug administration. Each participant will take the two drugs in a randomised crossover design. A wash-out period of two week between the two administration will be implemented.

• Study Type: Interventional
• Enrollment (Actual): 24
• Phase: Phase 4

Contacts and Locations

Study Locations

• Switzerland
  • Vaud
    • Lausanne, Vaud, Switzerland, 1004
      • Centre Hospitalier Universitaire Vaudois

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Tolerance to study drugs
• Age > 18 years
• Arteria hypertension stage 1-2 (blood pressure: 140/90 and 180/110 mm Hg)
• Normal renal function
• Availability to give informed consent

Exclusion Criteria:

• Intolerance to study drugs
• Renal artery stenosis
• Hyperkalaemia > 5.0 mmol/l
• Contra-indications to the use of PAH, inulin or Lithium
• Asthma
• Pychiatric illness
• No estimated easy vascular venous access for placement of two peripherical venous catheters in forearms
• Contra-indication to MRI-imaging: Claustrophobia or Pacemaker or other implanted metal device

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aliskiren; Aliskiren 150 to 300 mg once a Week for 8 weeks	Drug: Aliskiren; Drug therapy will be started with an initial 2 weeks on Aliskiren 150 mg followed by a titration to 300 mg Aliskiren if the treatment is well tolerated. A first baseline measurements will be performed before initiating therapy and a second after 8 weeks of treatment (24h after last drug intake) to assess the chronic effect.; Other Names: Rasilez
Active Comparator: Hydrochlorothiazide; HCTZ 12.5 - 25 mg/d once a day for 8 weeks	Drug: Hydrochlorothiazide; Drug therapy will be started with an initial 2 weeks HCTZ 12.5 mg followed by a titration to 25 mg HCTZ if the treatment is well tolerated. A first baseline measurements will be performed before initiating therapy and a second after 8 weeks of treatment (24h after last drug intake) to assess the chronic effect.; Other Names: Esidrex

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Renal Oxygenation Changes After Chronic Treatment With Aliskiren or Hydrochlorothiazide	Changes in R2* at between week 0 and week 8 as measured by BOLD MRI in the cortex and medulla of the kidney	week 0 vs week 8

Collaborators and Investigators

• Sponsor: Centre Hospitalier Universitaire Vaudois

Publications and helpful links

General Publications

• Pruijm M, Hofmann L, Maillard M, Tremblay S, Glatz N, Wuerzner G, Burnier M, Vogt B. Effect of sodium loading/depletion on renal oxygenation in young normotensive and hypertensive men. Hypertension. 2010 May;55(5):1116-22. doi: 10.1161/HYPERTENSIONAHA.109.149682. Epub 2010 Mar 22.
• Vakilzadeh N, Muller ME, Forni V, Milani B, Hoffman L, Piskunowicz M, Maillard M, Zweiacker C, Pruijm M, Burnier M. Comparative Effect of a Renin Inhibitor and a Thiazide Diuretic on Renal Tissue Oxygenation in Hypertensive Patients. Kidney Blood Press Res. 2015;40(5):542-54. doi: 10.1159/000368530. Epub 2015 Oct 26.

Study record dates

Study Major Dates

• Study Start: October 1, 2011
• Primary Completion (Actual): October 1, 2014
• Study Completion (Actual): October 1, 2014

Study Registration Dates

• First Submitted: January 6, 2012
• First Submitted That Met QC Criteria: January 24, 2012
• First Posted (Estimate): January 27, 2012

Study Record Updates

• Last Update Posted (Actual): March 17, 2020
• Last Update Submitted That Met QC Criteria: March 3, 2020
• Last Verified: March 1, 2020

More Information

Terms related to this study

• Keywords: Kidney oxygenation; Stage 1 or 2 hypertension; BOLD-IRM
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Antihypertensive Agents; Natriuretic Agents; Membrane Transport Modulators; Diuretics; Sodium Chloride Symporter Inhibitors; Hydrochlorothiazide
• Other Study ID Numbers: 2011DR3137