Hypertension
Conditions
Keywords
Kidney oxygenation, Stage 1 or 2 hypertension, BOLD-IRM
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).
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.
Interventions
DRUGAliskiren
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.
DRUGHydrochlorothiazide
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.
Sponsors
Centre Hospitalier Universitaire Vaudois
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
NONE
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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 |
Countries
Switzerland
Participant flow
Recruitment details
47 patients were screened in a single centre (service of Nephrology, CHUV, Lausanne)
Pre-assignment details
24 patients were enrolled but 4 were excluded because of the lack of adequate venous access or for other reasons.
Participants by arm
| Arm | Count |
|---|---|
| Aliskiren Patients with essential hypertension stage 1 and 2 . | 11 |
| HCTZ Patients with essential hypertension stage 1 and 2 | 9 |
| Total | 20 |
Withdrawals & dropouts
| Period | Reason | FG000 | FG001 |
|---|---|---|---|
| Overall Study | No possibility to put a catheter | 1 | 2 |
| Overall Study | Withdrawal by Subject | 0 | 1 |
Baseline characteristics
| Characteristic | Aliskiren | HCTZ | Total |
|---|---|---|---|
| Age, Continuous | 55.7 years STANDARD_DEVIATION 8.6 | 49.7 years STANDARD_DEVIATION 15 | 52.7 years STANDARD_DEVIATION 12 |
| blood pressure | 150 mmHg STANDARD_DEVIATION 10.7 | 141 mmHg STANDARD_DEVIATION 12.9 | 146 mmHg STANDARD_DEVIATION 11.5 |
| Ethnicity (NIH/OMB) Hispanic or Latino | 0 Participants | 0 Participants | 0 Participants |
| Ethnicity (NIH/OMB) Not Hispanic or Latino | 11 Participants | 8 Participants | 19 Participants |
| Ethnicity (NIH/OMB) Unknown or Not Reported | 0 Participants | 1 Participants | 1 Participants |
| Region of Enrollment Switzerland | 11 participants | 9 participants | 20 participants |
| Sex: Female, Male Female | 3 Participants | 3 Participants | 6 Participants |
| Sex: Female, Male Male | 8 Participants | 6 Participants | 14 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | — / — | — / — |
| other Total, other adverse events | 0 / 11 | 0 / 9 |
| serious Total, serious adverse events | 0 / 11 | 0 / 9 |
Outcome results
Primary
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
Time frame: week 0 vs week 8
| Arm | Measure | Group | Value (MEAN) | Dispersion |
|---|---|---|---|---|
| Aliskiren | Renal Oxygenation Changes After Chronic Treatment With Aliskiren or Hydrochlorothiazide | Cortex week 0 | 20.5 1/sec | Standard Error 1 |
| Aliskiren | Renal Oxygenation Changes After Chronic Treatment With Aliskiren or Hydrochlorothiazide | Cortex week 8 | 19.5 1/sec | Standard Error 1 |
| Hydrochlorothiazide | Renal Oxygenation Changes After Chronic Treatment With Aliskiren or Hydrochlorothiazide | Cortex week 0 | 19.5 1/sec | Standard Error 1 |
| Hydrochlorothiazide | Renal Oxygenation Changes After Chronic Treatment With Aliskiren or Hydrochlorothiazide | Cortex week 8 | 20.5 1/sec | Standard Error 1 |