RAS Peptide Profiles in Patients With Arterial Hypertension

NCT02449811 | Completed

• 1 other identifier: EKNZ 2015-081
• Study Type: observational
• Target: 107
• Locations: 1 country
• Sites: 1

Brief Summary

Randomized, open-label, parallel-group study conducted at a single center in Switzerland. Patients diagnosed with primary arterial hypertension requiring antihypertensive drug Treatment as well as patients after a 4 week wash out period (Amendment 07/2016) will be recruited at the University Hospital Basel, Switzerland. Subjects will be randomized to either the angiotensin-converting enzyme inhibitor-, angiotensin receptor blocker-, calcium channel blocker- or hydrochlorothiazide-treatment arm. Drug treatment follows current guidelines issued by the European Society of Hypertension. Treatment-naive patients will be started on an intermediate dose monotherapy (treatment period 1). In all patients who do not reach blood pressure targets after 4 weeks, the dose of the monotherapy drug will be doubled (high dose, treatment period 2). Sampling for the analysis of RAS peptide profiles, measurement of drug concentrations in plasma and non-invasive hemodynamic measurements will be done. A control group with 20 age and gender matched, healthy and normotensive subjects will be recruited to establish the characteristics of the RAS peptide profiles in a comparable but normotensive population.

Conditions

Essential Hypertension

Outcome Measures

Primary Outcomes (1)

• RAS peptide profiles

  Concentration measurement of the different RAS peptides

  0h and 4h

Secondary Outcomes (3)

• Composite measure of Non-invasive hemodynamic parameters

  0h and 4h

• Plasma renin activity and aldosterone concentration

  0h and 4h

• Antihypertensive drug concentrations

  0h and 4h

Study Arms (4)

Perindopril

Treatment period 1: Perindopril 5mg, oral, once daily, for 4 weeks Treatment period 2: Perindopril 10mg, oral, once daily, for 4 weeks

Drug: Perindopril

Olmesartan

Treatment period 1: Olmesartan 20mg, oral, once daily, for 4 weeks Treatment period 2: Olmesartan 40mg, oral, once daily, for 4 weeks

Drug: Olmesartan

Amlodipine

Treatment period 1: Amlodipine 5mg, oral, once daily, for 4 weeks Treatment period 2: Amlodipine 10mg, oral, once daily, for 4 weeks

Drug: Amlodipine

Hydrochlorothiazide

Treatment period 1: Hydrochlorothiazide 25mg, oral, once daily, for 4 weeks Treatment period 2: Hydrochlorothiazide 50mg, oral, once daily, for 4 weeks

Drug: Hydrochlorothiazide

Interventions

Perindopril DRUG

Perindopril

Olmesartan DRUG

Olmesartan

Amlodipine DRUG

Amlodipine

Hydrochlorothiazide DRUG

Hydrochlorothiazide

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Community sample

You may qualify if:

• Male or female outpatients with previously untreated non-secondary arterial hypertension, defined as: office-systolic blood pressure ≥ 140 mmHg and ≤ 180 mmHg and office-diastolic blood pressure ≥ 90 mmHg and ≤110 mmHg (ESH grade I and II hypertension).
• Male or female outpatients with previously treated non-secondary arterial Hypertension after a wash out period of 4 weeks (Amendment 07/2016)
• Evaluation of 24h blood pressure measurement fulfills criteria of hypertension: mean systolic blood pressure / diastolic blood pressure ≥ 130/80 on average, ≥ 135/85 during the day, or ≥ 120/70 during the night.
• Age ≥ 18 years
• Body mass index between 18 and 35 kg/m²
• Body weight at least 50 kg
• Ability to understand study procedures and to provide written informed consent
• Hematology and clinical chemistry results not deviating from the normal range to a clinically relevant extent at screening.
• lead ECG without clinically relevant abnormalities (Exception: signs of left ventricular hypertrophy with Sokolow index \>3.5mV).
• Female study participants less than one year post-menopausal must, be non-pregnant and non-lactating, and willing to use an adequate and highly effective method of contraception throughout the study and for 1 week after the last dose. A highly effective method of birth control is defined as those which result in a low failure rate (i.e. less than 1% per year) when used consistently and correctly such as, implants, injectables, combined oral contraceptives, some intrauterine devices (IUD) (hormonal) in combination with a condom or sterilisation, sexual abstinence or vasectomised partner.

You may not qualify if:

• Pregnant or lactating women
• Clinical chemistry results indicating secondary arterial hypertension.
• History of or clinically evident cardiovascular disease (other than arterial hypertension), namely myocardial infarction and valvular heart disease or heart failure.
• Ventricular or dual pacemaker wearers
• Uni- or bilateral renal artery stenosis
• Renal dysfunction, defined as estimated creatinine-clearance \< 60 ml/min
• Recipient of kidney transplant
• Moderate or severe hepatic impairment
• Clinically relevant lung disease (e.g. uncontrolled bronchial asthma, chronic obstructive pulmonary disease (COPD))
• History of alcohol abuse
• Loss of ≥ 250 ml of blood within 3 months prior to screening.
• Known hypersensitivity to any of the four antihypertensive drugs or any excipients of the drug formulations
• History or clinical evidence of any disease and / or existence of any surgical or medical condition, which might interfere with the absorption, distribution, metabolism or excretion of the study drugs, or which might increase the risk for toxicity.
• Participation in another clinical trial within past 30 days
• Any circumstances or conditions, which, in the opinion of the investigator, may affect full participation in the study or compliance with the protocol.

Sponsors & Collaborators

• Insel Gruppe AG, University Hospital Bern: lead

Study Sites (1)

University Hospital

Basel, 4031, Switzerland

Location

Biospecimen

Retention: SAMPLES WITHOUT DNA

plasma samples

MeSH Terms

Conditions

Essential Hypertension

Interventions

Perindopril; olmesartan; Amlodipine; Hydrochlorothiazide

Condition Hierarchy (Ancestors)

Hypertension; Vascular Diseases; Cardiovascular Diseases

Intervention Hierarchy (Ancestors)

Indoles; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Dihydropyridines; Pyridines; Heterocyclic Compounds, 1-Ring; Chlorothiazide; Benzothiadiazines; Sulfonamides; Sulfones; Sulfur Compounds; Organic Chemicals; Thiazides

Study Officials

• Manuel Haschke, Prof. Dr. med.

  University of Bern

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: observational
• Observational Model: OTHER
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 10, 2015
• First Posted: May 20, 2015
• Study Start: April 1, 2015
• Primary Completion: August 1, 2018
• Study Completion: November 1, 2018
• Last Updated: February 22, 2019

Record last verified: 2019-02

Locations

CH (1)