Renal Effects of Intrarenal Nesiritide

This study has been terminated.
(Funding not available)
Sponsor:
Information provided by:
University of Maryland
ClinicalTrials.gov Identifier:
NCT00270829
First received: December 23, 2005
Last updated: February 8, 2008
Last verified: February 2008
  Purpose

The impact of nesiritide in CHF is unclear, but it is possible that systemic vasodilation leads to adverse consequences even if the direct renal effects are positive. Therefore, this study will look at the effects of direct intrarenal administration of nesiritide on GFR and RPF.


Condition Intervention Phase
Heart Failure, Congestive
Drug: nesiritide
Phase 4

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: Renal Effects of Intrarenal Nesiritide

Resource links provided by NLM:


Further study details as provided by University of Maryland:

Primary Outcome Measures:
  • GFR [ Time Frame: hours ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Urine output [ Time Frame: hours ] [ Designated as safety issue: No ]
  • RPF [ Time Frame: hours ] [ Designated as safety issue: No ]
  • sodium excretion [ Time Frame: hours ] [ Designated as safety issue: No ]

Enrollment: 2
Study Start Date: December 2005
Study Completion Date: January 2007
Primary Completion Date: January 2007 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: 1
Nesiritide given intrarenally
Drug: nesiritide
Drug given intrarenally or placebo
No Intervention: 2
No intrarenal drug administration

Detailed Description:

We will perform an open-label, parallel arm, controlled study of intrarenal nesiritide in 26 patients hospitalized with CHF. Patients will be admitted for CHF exacerbation and randomly but equally divided into treatment and placebo groups. Both arms will receive diuretics on admission as dictated by clinical need. They will then have an 8-hour diuretic-free period (overnight). Each arm will then have renal parameters (GFR, RPF, urine output, urinary sodium excretion) assessed using PAH and iothalamate. These parameters will be measured prior to administration of drug during period 1. Randomization will be performed via an interactive computerized call in program following completion of screening procedures and once patient has given informed consent.

At time 0, treatment patients will be taken to the cardiac catheterization lab for placement of the Benephit Infusion System (Flow Medica). Placement involves femoral artery cannulation and introduction of a bifurcated infusion catheter into the arterial system to a destination at the level of renal arteries. This will be done under fluoroscopic guidance.

When placement of catheter is completed, period 2 will begin with initiation of Study Drug infusion (IR nesiritide or IV D5W). Nesiritide will be diluted according to its labeled instructions in D5W to a final dilution of 6 mcg/mL. Placebo patients will receive IV D5W as a bolus and a continuous infusion of D5W at volumes equal to what they would have gotten had they been randomized to nesiritide.

Intra-renal (IR) infusion of nesiritide will be given as a 2ug/kg bolus followed by an infusion of 0.01 mg/kg/min through the intrarenal catheter. The nesiritide infusion will continue for 6 hours.

Period 3 begins at the 3-hour mark, at which time, both the placebo and treatment groups will be treated with boluses of intravenous furosemide. Both treatment arms will receive furosemide at this time. Blood drawn at 3 and 6 hours and urine collected between 3 and 6 hours will be used to determine GFR, RPF, Na excretion and urine output.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • Hospitalized for worsening CHF and volume overload
  • Creatinine increased by greater than or equal to 0.2 and greater than or equal to 10% above baseline at study initiation
  • Age greater than or equal to 18 years
  • NHYA class II-IV at the time of initiation in the study
  • EF less than or equal to 40%
  • Signed Informed Consent

Exclusion Criteria:

  • Current or anticipated need for dialysis during the study period
  • Systolic blood pressure less than or equal to 90 mmHg
  • Calculated CrCL based on Cockcroft-Gault less than or equal to 15 cc/min
  • Hypersensitivity to nesiritide
  • Cardiogenic shock
  • Clinically significant aortic or mitral stenosis
  • Contraindication to vasodilator treatment
  • Inability to withstand 11-15 hours without diuretics
  • Suspected renal deterioration due to causes unrelated to CHF such as radiocontrast administration, NSAID use
  • Receipt of dose of NSAID within 12 hours of study drug initiation
  • Use of radiocontrast media within 7 days of study drug initiation (other than the small amount of IV contrast that will be needed to place intrarenal catheter to the level of the renal artery)
  • Use of nephrotoxic drugs such as aminoglycosides or cisplatinum within 7 days of study initiation
  • Use of sildenafil or other PDE5 inhibitors within 24 hours of study drug initiation
  • Diseases of weak collagen (i.e. Marfans)
  • Aortic or renal aneurysm
  • Significant calcification in the region of the renal ostia, or any other condition that would, in the opinion of the investigator, increase risk of placement of an intravascular sheath and catheter.
  • Known bleeding diathesis
  • Solitary kidney or solitary functioning kidney
  • Known uncorrected renal artery stenosis greater than 50% in either renal artery.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00270829

Locations
United States, Maryland
University of Maryland
Baltimore, Maryland, United States, 21201
Sponsors and Collaborators
University of Maryland
Investigators
Principal Investigator: Stephen S Gottlieb University of Maryland
  More Information

No publications provided

Responsible Party: Stephen Gottlieb, University of MD
ClinicalTrials.gov Identifier: NCT00270829     History of Changes
Other Study ID Numbers: H-26854
Study First Received: December 23, 2005
Last Updated: February 8, 2008
Health Authority: United States: Institutional Review Board

Keywords provided by University of Maryland:
renal function

Additional relevant MeSH terms:
Heart Failure
Heart Diseases
Cardiovascular Diseases
Natriuretic Peptide, Brain
Natriuretic Agents
Physiological Effects of Drugs
Pharmacologic Actions
Cardiovascular Agents
Therapeutic Uses

ClinicalTrials.gov processed this record on September 22, 2014