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Nesiritide in Hypertension (TENSE1)

Primary Purpose

Hypertension

Status
Recruiting
Phase
Phase 1
Locations
Norway
Study Type
Interventional
Intervention
Nesiritide
Placebo
Sponsored by
Oslo University Hospital
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Hypertension

Eligibility Criteria

18 Years - 79 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Office systolic blood pressure (SBP) ≥ 120 mmHg and treatment with at least one anti-hypertensive medication. Unchanged medication regimen the last two weeks prior to inclusion.
  • Average day-time SBP > 115 on a 24-h ambulatory BP measurement at screening.

Exclusion Criteria:

  • Congestive Heart Failure (any New York Heart Association class)
  • Ejection Fraction ≤ 40 %
  • Known, not appropriately treated, secondary hypertension
  • Myocardial infarction within 3 months of screening
  • Unstable angina within 14 days of screening, or any evidence of myocardial ischemia
  • Pulmonary hypertension
  • Aortic stenosis with maximum jet velocity > 2,5 m/s
  • Other valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis or biopsy proven active myocarditis
  • Sustained Ventricular Tachycardia or Ventricular Fibrillation within 14 days of screening
  • Sustained Atrial Fibrillation
  • Second or third degree atrioventricular block without a permanent cardiac pacemaker
  • Cerebrovascular event within 3 months of screening, or other evidence of significantly compromised cerebral perfusion
  • Proteinuria defined as albumin:creatinine ratio > 100 (equivalent to an excretion of > 1 g/day)
  • Nephrotic syndrome
  • Body Mass Index > 35
  • Total bilirubin of > 25 µmol/L, aspartate aminotransferase or alanine aminotransferase 1.5 times the upper limit of normal range
  • Renal insufficiency assessed by estimated glomerular filtration rate (GFR) < 30 ml/min
  • Serum sodium of ≤ 135 mmol/L and ≥ 150 mmol/L
  • Serum potassium of ≤ 3.5 mmol/L and ≥ 5.5 mmol/L
  • Women taking hormonal contraceptives containing estrogens
  • Pregnancy
  • Patients on prolonged, i.e. more than 30 days, immunosuppressant therapy
  • Patients with known, active malignancies
  • Patients with orthostatic hypotension
  • Participation in a trial with an investigational product within the previous three months
  • Any contraindication listed on the Investigator's Brochure of the Investigational Medicinal Product
  • Any reason why, in the opinion of the investigator, the patient should not participate.

Sites / Locations

  • Oslo University Hopital, Rikshospitalet
  • Oslo University Hospital, Ullevål HospitalRecruiting
  • Akershus University HospitalRecruiting

Arms of the Study

Arm 1

Arm 2

Arm Type

Active Comparator

Placebo Comparator

Arm Label

Subcutaneous BNP

Subcutaneous placebo

Arm Description

Patients will receive gradually increasing doses (10-25 µg/kg) of subcutaneously administered nesiritide (BNP) twice daily for two days, to determine the feasibility, safety and blood pressure lowering effect of BNP so as to identify the optimal dose.

Patients will receive subcutaneously administered placebo twice daily for two days for determination of the effect of BNP.

Outcomes

Primary Outcome Measures

Changes in blood pressure (BP)
Office blood pressure and ambulatory blood pressure monitoring (ABPM) recordings will be used for the analysis

Secondary Outcome Measures

Renal function as assessed by estimated glomerular filtration rate (eGFR)
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-cystatin C equation will be used to calculate estimated glomerular filtration rate (eGFR).
Hormonal changes assessed by aldosterone, atrial natriuretic peptide (ANP), N Terminal-ANP, BNP, N Terminal-proBNP, C-type natriuretic peptide and cyclic guanosyl monophosphate.
Will be measured in plasma, and all but aldosterone in urine Collections.
Number of participants with treatment-related adverse events defined as all untoward and unintended responses to the treatment related to any dose administered.

Full Information

First Posted
November 9, 2015
Last Updated
December 29, 2017
Sponsor
Oslo University Hospital
Collaborators
University of Oslo, University Hospital, Akershus
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1. Study Identification

Unique Protocol Identification Number
NCT02608996
Brief Title
Nesiritide in Hypertension
Acronym
TENSE1
Official Title
Therapeutic Effects of BNP in Hypertensive Patients
Study Type
Interventional

2. Study Status

Record Verification Date
December 2017
Overall Recruitment Status
Recruiting
Study Start Date
December 2015 (undefined)
Primary Completion Date
December 2018 (Anticipated)
Study Completion Date
December 2030 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Oslo University Hospital
Collaborators
University of Oslo, University Hospital, Akershus

4. Oversight

Data Monitoring Committee
Yes

5. Study Description

Brief Summary
Hypertension remains a global burden in cardiovascular disease leading to stroke, myocardial infarction, and heart failure. Its myocardial complications result from increased mechanical load on the heart. Under physiological conditions of increased myocardial load and resulting myocardial stretch, atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) synthesis and secretion occur contributing to maintenance of optimal cardiorenal and blood pressure homeostasis. However, studies indicate that in subjects with cardiovascular diseases the biological structure of these hormones may be altered, thus reducing their favorable protective activities. New studies indicate that early and moderate hypertension is associated with a derangement of the natriuretic peptide system which is characterized by the lack of activation of biologically active ANP and BNP, while severe hypertension is characterized by cardiac release of altered molecular forms of ANP and BNP that have reduced biological properties and/or enhanced degradation. The broad objective of this proposal is to advance the biology and therapeutics of the NPs with a special focus on the cardiac peptide BNP in human hypertension. Our proposal is based upon the biological properties of BNP (i.e. natriuretic, renin-angiotensin-aldosterone suppressing, vasodilating, anti-fibrotic, anti-hypertrophic and positive lusitropic), its mechanistic role in human hypertension, and thus its potential as an innovative chronic protein therapeutic to enhance the treatment of patients with hypertension. Importantly, BNP is an endocrine hormone normally produced by the human heart, and it has been approved for the treatment of acute heart failure in USA.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Hypertension

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
Participant
Allocation
Randomized
Enrollment
15 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title
Subcutaneous BNP
Arm Type
Active Comparator
Arm Description
Patients will receive gradually increasing doses (10-25 µg/kg) of subcutaneously administered nesiritide (BNP) twice daily for two days, to determine the feasibility, safety and blood pressure lowering effect of BNP so as to identify the optimal dose.
Arm Title
Subcutaneous placebo
Arm Type
Placebo Comparator
Arm Description
Patients will receive subcutaneously administered placebo twice daily for two days for determination of the effect of BNP.
Intervention Type
Drug
Intervention Name(s)
Nesiritide
Other Intervention Name(s)
Natrecor, BNP
Intervention Description
This intervention is designed to determine the optimal dose range of BNP for treatment of patients with uncontrolled hypertension
Intervention Type
Drug
Intervention Name(s)
Placebo
Other Intervention Name(s)
Saline solution
Intervention Description
For comparison to elucidate the true effect of nesiritide
Primary Outcome Measure Information:
Title
Changes in blood pressure (BP)
Description
Office blood pressure and ambulatory blood pressure monitoring (ABPM) recordings will be used for the analysis
Time Frame
48 hours, from day 1 to day 2. Specifically, it will be assessed before first injection(baseline data) up to 12 hours post last injection.
Secondary Outcome Measure Information:
Title
Renal function as assessed by estimated glomerular filtration rate (eGFR)
Description
Chronic Kidney Disease Epidemiology Collaboration (CKD-EPI) creatinine-cystatin C equation will be used to calculate estimated glomerular filtration rate (eGFR).
Time Frame
48 hours, from day 1 to day 2. Specifically, it will be assessed before first injection (baseline data) up to 12 hours post last injection.
Title
Hormonal changes assessed by aldosterone, atrial natriuretic peptide (ANP), N Terminal-ANP, BNP, N Terminal-proBNP, C-type natriuretic peptide and cyclic guanosyl monophosphate.
Description
Will be measured in plasma, and all but aldosterone in urine Collections.
Time Frame
48 hours, from day 1 to day 2. Specifically, it will be assessed before first injection (baseline data) up to 12 hours post last injection.
Title
Number of participants with treatment-related adverse events defined as all untoward and unintended responses to the treatment related to any dose administered.
Time Frame
48 hours, from day 1 to day 2. Specifically, it will be assessed after first injection, up to 12 hours post last injection. A second determination will be done within 3 weeks after last injection (21 days assessment).

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
79 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Office systolic blood pressure (SBP) ≥ 120 mmHg and treatment with at least one anti-hypertensive medication. Unchanged medication regimen the last two weeks prior to inclusion. Average day-time SBP > 115 on a 24-h ambulatory BP measurement at screening. Exclusion Criteria: Congestive Heart Failure (any New York Heart Association class) Ejection Fraction ≤ 40 % Known, not appropriately treated, secondary hypertension Myocardial infarction within 3 months of screening Unstable angina within 14 days of screening, or any evidence of myocardial ischemia Pulmonary hypertension Aortic stenosis with maximum jet velocity > 2,5 m/s Other valvular stenosis, hypertrophic, restrictive or obstructive cardiomyopathy, constrictive pericarditis or biopsy proven active myocarditis Sustained Ventricular Tachycardia or Ventricular Fibrillation within 14 days of screening Sustained Atrial Fibrillation Second or third degree atrioventricular block without a permanent cardiac pacemaker Cerebrovascular event within 3 months of screening, or other evidence of significantly compromised cerebral perfusion Proteinuria defined as albumin:creatinine ratio > 100 (equivalent to an excretion of > 1 g/day) Nephrotic syndrome Body Mass Index > 35 Total bilirubin of > 25 µmol/L, aspartate aminotransferase or alanine aminotransferase 1.5 times the upper limit of normal range Renal insufficiency assessed by estimated glomerular filtration rate (GFR) < 30 ml/min Serum sodium of ≤ 135 mmol/L and ≥ 150 mmol/L Serum potassium of ≤ 3.5 mmol/L and ≥ 5.5 mmol/L Women taking hormonal contraceptives containing estrogens Pregnancy Patients on prolonged, i.e. more than 30 days, immunosuppressant therapy Patients with known, active malignancies Patients with orthostatic hypotension Participation in a trial with an investigational product within the previous three months Any contraindication listed on the Investigator's Brochure of the Investigational Medicinal Product Any reason why, in the opinion of the investigator, the patient should not participate.
Central Contact Person:
First Name & Middle Initial & Last Name or Official Title & Degree
Alessandro Cataliotti, MD, PhD
Phone
+47 23016807
Email
alessandro.cataliotti@medisin.uio.no
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Alessandro Cataliotti, MD, PhD
Organizational Affiliation
Oslo University Hospital and University of Oslo
Official's Role
Principal Investigator
Facility Information:
Facility Name
Oslo University Hopital, Rikshospitalet
City
Oslo
ZIP/Postal Code
0424
Country
Norway
Individual Site Status
Not yet recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Hassan Z Khiabani, MD, PhD
First Name & Middle Initial & Last Name & Degree
Hassan Z Khiabani, MD, PhD
Facility Name
Oslo University Hospital, Ullevål Hospital
City
Oslo
ZIP/Postal Code
0450
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
Morten Rostrup, MD, PhD
First Name & Middle Initial & Last Name & Degree
Kaja K Bergo, MD
First Name & Middle Initial & Last Name & Degree
Morten Rostrup, MD, PhD
First Name & Middle Initial & Last Name & Degree
Einar S Norden
First Name & Middle Initial & Last Name & Degree
Ivar Sjaastad, MD, PhD
Facility Name
Akershus University Hospital
City
Strømmen
ZIP/Postal Code
1478
Country
Norway
Individual Site Status
Recruiting
Facility Contact:
First Name & Middle Initial & Last Name & Degree
My HS Svensson, MD, PhD
First Name & Middle Initial & Last Name & Degree
My HS Svensson, MD, PhD
First Name & Middle Initial & Last Name & Degree
Helge Røsjø, MD, PhD

12. IPD Sharing Statement

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Nesiritide in Hypertension

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