Sodium Nitroprusside for Blood Pressure Reduction in the ICU (SNP2) - Full Text View

Purpose

Nitroprusside is used commonly in the Intensive Care Unit for long periods of time in order to reduce blood pressure. It is not known if the body compensates over time to the blood pressure lowering, and if when the nitroprusside is stopped the blood pressure goes up at a faster rate and is higher than it was at the start of the treatment. This study will answer these questions.

Condition	Intervention	Phase
Hypertension	Drug: nitroprusside Drug: placebo infusion	Phase 2

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Safety/Efficacy Study Intervention Model: Single Group Assignment Masking: Double Blind (Subject, Caregiver, Investigator) Primary Purpose: Treatment
Official Title:	A Phase 2, Multicenter, Randomized, Double-blind, Placebo-controlled, Parallel Group Study to Determine the Pharmacodynamics of Sodium Nitroprusside During Prolonged Infusion in Pediatric Subjects

Resource links provided by NLM:

MedlinePlus related topics: High Blood Pressure

Drug Information available for: Sodium nitroprusside Nitroprusside

U.S. FDA Resources

Further study details as provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

Primary Outcome Measures:

The primary endpoint is the change in MAP during the Blinded Study Drug Administration Phase in the absence of other stimuli. [ Time Frame: 8 months ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

1. To compare the proportion of patients randomized to receive either sodium nitroprusside or placebo who experience offset during the 30-minute blinded study drug period. [ Time Frame: 8 months ] [ Designated as safety issue: No ]
2. To compare the proportion of patients randomized to receive either sodium nitroprusside or placebo who experience rebound hypertension during blinded study drug period [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]
3. To compare the proportion of patients randomized to receive either sodium nitroprusside or placebo who experience a serious adverse event during the 30-minute blinded study drug period [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]
4. To compare the distribution of patients randomized to receive either sodium nitroprusside or placebo who experience a treatment-emergent and related adverse event, by maximum severity grade, during the 30-minute blinded study drug period. [ Time Frame: 8 months ] [ Designated as safety issue: Yes ]
5. To compare the changes in vital signs (systolic blood pressure, diastolic blood pressure, MAP, and heart rate) between patients randomized to receive either sodium nitroprusside or placebo [ Time Frame: 8 months ] [ Designated as safety issue: No ]
6. To compare the changes in individual laboratory parameters between patients randomized to receive either sodium nitroprusside or placebo. [ Time Frame: 8 months ] [ Designated as safety issue: No ]

Enrollment:	45
Study Start Date:	January 2009
Study Completion Date:	January 2011
Primary Completion Date:	January 2011 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
Active Comparator: 1 Blinded nitroprusside infusion	Drug: nitroprusside nitroprusside continuous infusion, dose to be titrated to clinical effect Other Name: Nipride
Placebo Comparator: 2 Blinded placebo infusion	Drug: placebo infusion blinded placebo infusion, to be infused at same rate as open-label nitroprusside infusion

Detailed Description:

This is a phase 2, multicenter, randomized, double-blind placebo-controlled, parallel group study to determine the persistence of the effect of SNP on blood pressure and to assess the potential for rebound hypertension associated with prolonged infusion in pediatric subjects.

The primary endpoint is the change in MAP during the Blinded Study Drug Administration Phase in the absence of other stimuli.

Eligibility

Ages Eligible for Study:	up to 17 Years
Genders Eligible for Study:	Both
Accepts Healthy Volunteers:	No

Criteria

Inclusion Criteria:

Subject is less than 17 years of age.
An in-dwelling arterial line is clinically indicated.
Subject's parent or legal guardian is willing and able to give informed parental permission signing and dating an IRB-approved informed parental permission containing all of the elements of informed consent, and subject provides assent, signing an IRB-approved and -required informed assent, if applicable.
Subject is anticipated to require a minimum of 20 mm Hg (15 mm Hg for subjects < 2 years old) reduction in MAP for at least 12 hours using SNP [i.e., MAPB1 - MAPB2 ≥ 20 mm Hg (15 mm Hg for subjects < 2 years old)]

Exclusion criteria:

Subject weighs < 3.0 kg.
Subject has a known allergy to SNP.
Subject has a known mitochondrial cytopathy with a disorder of oxidative phosphorylation or of respiratory chain enzymes.
Subject has a contraindication to vasodilator therapy for control of blood pressure during surgery or in the intensive care unit.
Subject has raised intracranial pressure.
Subject is anticipated to need anti-hypertensive drugs other than Sodium Nitroprusside either IV (e.g. dexmedetomidine, esmolol, etc.) or epidural (e.g.local anesthetics, clonidine, etc.) within three terminal half-lives (3X T½ β) of the blinded study drug period. However, patients receiving stable doses of an anti-hypertensive drug(s) prior to the initiation of study drug may be enrolled.
Subject has any serious medical condition which, in the opinion of the investigator, is likely to interfere with study procedures.
Subject is moribund (death likely to occur within 48 hours).
Subject has a positive result for the urine or serum HCG test administered at screening.
Subject has participated in other clinical trials for investigational drugs within 30 days prior to enrollment
Subject has received or will have received Sodium Thiosulfate within 6 hours prior to the start of the open-label period.
Subject is either on, or anticipated to be on, ECMO.

Contacts and Locations

Please refer to this study by its ClinicalTrials.gov identifier: NCT00621816

Locations

United States, Arkansas
Arkansas Children's Hospital
Little Rock, Arkansas, United States, 72202
United States, California
Stanford University School of Medicine
Stanford, California, United States, 94305
United States, Kentucky
Kosair Charities Pediatric Clinical Research Unit
Louisville, Kentucky, United States, 40202
United States, Michigan
University of Michigan - Mott Children's Hospital
Ann Arbor, Michigan, United States, 48109-0243
United States, North Carolina
University of North Carolina - Chapel Hill
Chapel Hill, North Carolina, United States, 27500
Duke University Medical Center
Durham, North Carolina, United States, 27710
Duke University Medical Center
Durham, North Carolina, United States, 27705
United States, West Virginia
West Virginia University
Morgantown, West Virginia, United States, 26506

Sponsors and Collaborators

Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Investigators

Principal Investigator:	Scott Schulman, MD	Duke University
Principal Investigator:	Greg Hammer, MD	Stanford University

More Information

No publications provided

Responsible Party:	Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
ClinicalTrials.gov Identifier:	NCT00621816 History of Changes
Other Study ID Numbers:	N01-HD-4-3386, NICHD-2003-09-DR
Study First Received:	February 20, 2008
Last Updated:	December 2, 2011
Health Authority:	United States: Food and Drug Administration

Keywords provided by Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD):

nitroprusside
intensive care unit
hypertension
blood pressure reduction

Additional relevant MeSH terms:

Hypertension
Vascular Diseases
Cardiovascular Diseases
Nitroprusside
Vasodilator Agents
Cardiovascular Agents

Therapeutic Uses
Pharmacologic Actions
Nitric Oxide Donors
Molecular Mechanisms of Pharmacological Action
Antihypertensive Agents

ClinicalTrials.gov processed this record on May 16, 2013