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

• Sponsor: Centre Hospitalier Universitaire Vaudois (Other)
• Overall Status: Completed
• CT.gov ID: NCT01519635
• Collaborator: (none)
• Enrollment: 24
• Location: 1
• Arms: 2
• Duration (Months): 36
• Patients Per Site Per Month: 0.7

Study Details

Study Description

Brief Summary

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).

Condition or Disease	Intervention/Treatment	Phase
Hypertension	Drug: Aliskiren; Drug: Hydrochlorothiazide	Phase 4

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 Design

• Study Type: Interventional
• Actual Enrollment: 24 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Effect of Aliskiren 300mg and Hydrochlorothiazide 25mg on Kidney Oxygenation in Patients With Stage 1 and 2 Hypertension: a BOLD-MRI Study
• Study Start Date: Oct 1, 2011
• Actual Primary Completion Date: Oct 1, 2014
• Actual Study Completion Date: Oct 1, 2014

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures

1. Renal Oxygenation Changes After Chronic Treatment With Aliskiren or Hydrochlorothiazide [week 0 vs week 8]

   Changes in R2* at between week 0 and week 8 as measured by BOLD MRI in the cortex and medulla of the kidney

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: Yes

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

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Centre Hospitalier Universitaire Vaudois	Lausanne	Vaud	Switzerland	1004

Sponsors and Collaborators

• Centre Hospitalier Universitaire Vaudois

Investigators

• Principal Investigator: Michel Burnier, Professor, Centre Hospitalier Universitaire Vaudois

Study Documents (Full-Text)

None provided.

More Information

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.

• Responsible Party: Michel Burnier, Professor, Centre Hospitalier Universitaire Vaudois
• ClinicalTrials.gov Identifier: NCT01519635
• Other Study ID Numbers: 2011DR3137
• First Posted: Jan 27, 2012
• Last Update Posted: Mar 17, 2020
• Last Verified: Mar 1, 2020

• Keywords provided by Michel Burnier, Professor, Centre Hospitalier Universitaire Vaudois: Kidney oxygenation; Stage 1 or 2 hypertension; BOLD-IRM
• Additional relevant MeSH terms: Hypertension; Hydrochlorothiazide

Study Results

Participant Flow

Recruitment Details	47 patients were screened in a single centre (service of Nephrology, CHUV, Lausanne)
Pre-assignment Detail	24 patients were enrolled but 4 were excluded because of the lack of adequate venous access or for other reasons.

Arm/Group Title	Aliskiren	Hydrochlorothiazide
Arm/Group Description	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. 11 patients were enrolled and completed the study	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. Finally 9 patients were enrolled and completed the study
Period Title: Overall Study
STARTED	12	12
COMPLETED	11	9
NOT COMPLETED	1	3

Baseline Characteristics

Arm/Group Title	Aliskiren	HCTZ	Total
Arm/Group Description	Patients with essential hypertension stage 1 and 2 .	Patients with essential hypertension stage 1 and 2	Total of all reporting groups
Overall Participants	11	9	20
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	55.7 (8.6)	49.7 (15)	52.7 (12)
Sex: Female, Male (Count of Participants)
Female	3 27.3%	3 33.3%	6 30%
Male	8 72.7%	6 66.7%	14 70%
Ethnicity (NIH/OMB) (Count of Participants)
Hispanic or Latino	0 0%	0 0%	0 0%
Not Hispanic or Latino	11 100%	8 88.9%	19 95%
Unknown or Not Reported	0 0%	1 11.1%	1 5%
Region of Enrollment (participants) [Number]
Switzerland	11 100%	9 100%	20 100%
blood pressure (mmHg) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [mmHg]	150 (10.7)	141 (12.9)	146 (11.5)

Outcome Measures

1. Primary Outcome

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

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Aliskiren	Hydrochlorothiazide
Arm/Group Description	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.	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.
Measure Participants	11	9
Cortex week 0	20.5 (1)	19.5 (1)
Cortex week 8	19.5 (1)	20.5 (1)

Adverse Events

Arm/Group Title	Aliskiren		Hydrochlorothiazide
Arm/Group Description	Aliskiren: Drug therapy has been 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.		Hydrochlorothiazide: Drug therapy has been 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. No side effect were observed and all patients finished the sudy in this treatment arm
All Cause Mortality
	Aliskiren		Hydrochlorothiazide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Aliskiren		Hydrochlorothiazide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/9 (0%)
Other (Not Including Serious) Adverse Events
	Aliskiren		Hydrochlorothiazide
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/11 (0%)		0/9 (0%)

Limitations/Caveats

Small number of patients who completed the study. Overall underpowered.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.