Aliskiren on Retinal Vasculature Treatment Study

NCT01318395 | Completed Phase 3 DMC

• 1 other identifier: CSPP100ADE07T
• Study Type: interventional
• Target: 56
• Locations: 1 country
• Sites: 2

Brief Summary

Hypertension affects approximately one fourth of the world population and therefore contributes substantially to the worldwide burden of cardiovascular (CV) disease and end-organ damage. Changes in small artery structure characterized by an increased wall-to-lumen ratio (WLR) are characteristic feature of target organ damage in hypertension. Of clinical importance, structural arteries of small subcutaneous arteries have been shown to be of prognostic significance, with adverse prognosis in subjects with higher WLR. However, the assessment of arteriolar structure from biopsies of subcutaneous tissue is invasive and impractical in clinical practice. A new approach focuses on retinal arteriolar structural parameters by using scanning laser Doppler flowmetry (SLDF) with automatic full-field perfusion imaging analyses (9). This approach allows the non-invasive assessment of both the outer diameter (OD) and inner diameter (ID) of retinal arterioles in vivo and, thus, analyses vascular remodeling of retinal arterioles by calculating WLR = (OD - ID) / ID). A crucial role in the efforts of prevention of end-organ damage plays the renin angiotensin system (RAS). The increased mechanical strain on the vasculature at a higher BP can cause injury to the endothelial wall. Activation of the RAS increases BP and stimulates a local inflammatory response to repair the injury. Long-term or repeated response to injury leads to endothelial dysfunction and microvascular damage, and hence end-organ damage. Combining RAS inhibitors may provide greater end-organ protection than use of either class alone. However, ONTARGET has failed to show superiority of the dual RAS blockade (ACE-I and ARB) in patients at high cardiovascular risk. The combination of ARBs and direct renin inhibitors (DRIs) emerged as the only available, valid and innovative option for blocking the RAS at two different sites (sequential blockade). Indeed, AVOID study and ALLAY study demonstrated that the DRI aliskiren has additional and to some extent blood pressure independent effects on albuminuria and left ventricular hypertrophy, both signs of subclinical organ damage in hypertension, respectively. However, no data are available with respect to the effects of ARBs and DRIs on vascular properties in the short and long term To close this gab we focus in this study on vascular structural and functional changes since vascular adaptation to high blood pressure occurs in the early phase of hypertensive disease.

Conditions

Arterial Hypertension

Outcome Measures

Primary Outcomes (1)

• To investigate the combined effect of aliskiren and valsartan on vascular structure, assessed by wall to lumen ratio of retinal arterioles, in hypertensive patients.

  WLR = (outer diameter - inner diameter) / inner diameter) of retinal arterioles

  After 8 weeks of treatment with aliskiren versus placebo

Study Arms (2)

Aliskiren

ACTIVE COMPARATOR

Drug: Aliskiren

Placebo

PLACEBO COMPARATOR

Drug: Placebo

Interventions

Aliskiren DRUG

orally 150 mg/d for 1 week, then orally 300 mg/d for 7 weeks

Also known as: Rasilez

Aliskiren

Placebo DRUG

orally once per day

Placebo

Eligibility Criteria

• Age: 18 Years - 75 Years
• Sex: male
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Male or female aged 18 to 75 years (females of child bearing potential must be using adequate contraceptive precautions)
• Females of childbearing potential or within two years of the menopause must have a negative urine pregnancy test at enrolment visit
• Patients with mild to moderate uncomplicated essential hypertension with a trough mean sitting DBP ≥ 90 mmHg and/or SBP ≥ 140 mmHg or pretreated arterial hypertension
• Written informed consent
• Agreement to attend all study visits as planned in the protocol
• Agreement to perform routinely self home blood pressure measurements as well as keep a blood pressure diary throughout the study and to inform the investigator if BP exceeds cutt off criteria given in the ICF

You may not qualify if:

• In the investigator's opinion the patient can not be withdrawn from their current antihypertensive medication
• Secondary hypertension (e.g. patients with hyperaldosteronism, pheochromocytoma, renal artery stenosis, renal parenchymal disease, coarctation of the aorta, Cushing's disease syndrome)
• Severe essential hypertension (systolic blood pressure ≥ 180 mmHg and/or diastolic blood pressure ≥ 110 mmHg) or treatment resistant hypertension (3 antihypertensive drugs and still SBP ≥ 140mmHg and/or DBP ≥ 90mmHg)
• History of hypertensive encephalopathy or intracerebral hemorrhage
• Diabetes mellitus Type 1 or Type 2
• History of epilepsia (no retinal exam possible)
• Eye cataract (no retinal exam possible)
• History of the following within the last six months: myocardial infarction, unstable angina pectoris, percutaneous coronary intervention, heart failure
• Presence of significant renal, respiratory, hepatic, gastrointestinal, endocrine or metabolic, immunological, haematological or oncological, neurological and psychiatric diseases or dysfunction
• Impaired renal function as shown by estimated GFR (abbreviated MDRD formula) \< 45 ml/min/1.73 m2
• Impaired hepatic function as shown by transaminases higher than three times the upper normal limit
• Known allergy or a known intolerance to any ARB or Aliskiren
• Females who are pregnant or lactating or who are not on an adequate contraception (Pearl-Index ≥ 1 %)
• Use of any investigational drug within 28 days before study entry
• Patients previously enrolled into the study

Sponsors & Collaborators

• University of Erlangen-Nürnberg Medical School: lead

Study Sites (2)

Clinical Research Unit, Department of Nephrology and Hypertension, University of Erlangen-Nürnberg

Erlangen, 91054, Germany

Location

Clinical Research Unit, Department of Nephrology and Hypertension, University of Erlangen-Nürnberg

Nuremberg, 90471, Germany

Location

Related Publications (3)

• Jumar A, Ott C, Kistner I, Friedrich S, Schmidt S, Harazny JM, Schmieder RE. Effect of aliskiren on vascular remodelling in small retinal circulation. J Hypertens. 2015 Dec;33(12):2491-9. doi: 10.1097/HJH.0000000000000735.

  PMID: 26398851 RESULT

• Bosch A, Schmid A, Ott C, Kannenkeril D, Karg MV, Ditting T, Veelken R, Uder M, Schmieder RE. Copeptin Levels in Patients With Treatment-Resistant Hypertension Before and 6 Months After Renal Denervation. Am J Hypertens. 2020 Feb 22;33(2):182-189. doi: 10.1093/ajh/hpz155.

  PMID: 31555795 DERIVED

• Bosch AJ, Harazny JM, Kistner I, Friedrich S, Wojtkiewicz J, Schmieder RE. Retinal capillary rarefaction in patients with untreated mild-moderate hypertension. BMC Cardiovasc Disord. 2017 Dec 21;17(1):300. doi: 10.1186/s12872-017-0732-x.

  PMID: 29268712 DERIVED

MeSH Terms

Conditions

Hypertension

Interventions

aliskiren

Condition Hierarchy (Ancestors)

Vascular Diseases; Cardiovascular Diseases

Study Officials

• Roland E Schmieder, MD

  University of Erlangen-Nürnberg

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, INVESTIGATOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Prof. Dr. med.

Study Record Dates

• First Submitted: March 17, 2011
• First Posted: March 18, 2011
• Study Start: May 1, 2010
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: January 12, 2018

Record last verified: 2018-01

Locations

DE (2)