Clinical trial NCT00621816: Sodium Nitroprusside for Blood Pressure Reduction in the ICU (SNP2)
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
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE2
Conditions: Hypertension
Keywords: nitroprusside
intensive care unit
hypertension
blood pressure reduction
Lead sponsor: Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Sponsor class: NIH
First posted: 2008-02-22
Enrollment: 45
Sex: ALL
Minimum age (years): 1
Maximum age (years): 17
Standard ages: CHILD
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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.

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 criteria: Inclusion Criteria:

1. Subject is less than 17 years of age.
2. An in-dwelling arterial line is clinically indicated.
3. 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.
4. 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:

1. Subject weighs \< 3.0 kg.
2. Subject has a known allergy to SNP.
3. Subject has a known mitochondrial cytopathy with a disorder of oxidative phosphorylation or of respiratory chain enzymes.
4. Subject has a contraindication to vasodilator therapy for control of blood pressure during surgery or in the intensive care unit.
5. Subject has raised intracranial pressure.
6. 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.
7. Subject has any serious medical condition which, in the opinion of the investigator, is likely to interfere with study procedures.
8. Subject is moribund (death likely to occur within 48 hours).
9. Subject has a positive result for the urine or serum HCG test administered at screening.
10. Subject has participated in other clinical trials for investigational drugs within 30 days prior to enrollment
11. Subject has received or will have received Sodium Thiosulfate within 6 hours prior to the start of the open-label period.
12. Subject is either on, or anticipated to be on, ECMO.

Primary outcomes:
measure: The primary endpoint is the change in MAP during the Blinded Study Drug Administration Phase in the absence of other stimuli.
timeFrame: 8 months
Secondary outcomes:
measure: 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.
timeFrame: 8 months
measure: 2. To compare the proportion of patients randomized to receive either sodium nitroprusside or placebo who experience rebound hypertension during blinded study drug period
timeFrame: 8 months
measure: 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
timeFrame: 8 months
measure: 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.
timeFrame: 8 months
measure: 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
timeFrame: 8 months
measure: 6. To compare the changes in individual laboratory parameters between patients randomized to receive either sodium nitroprusside or placebo.
timeFrame: 8 months
Other outcomes:
Locations:
city: Little Rock
country: United States
facility: Arkansas Children's Hospital
state: Arkansas
city: Stanford
country: United States
facility: Stanford University School of Medicine
state: California
city: Louisville
country: United States
facility: Kosair Charities Pediatric Clinical Research Unit
state: Kentucky
city: Ann Arbor
country: United States
facility: University of Michigan - Mott Children's Hospital
state: Michigan
city: Chapel Hill
country: United States
facility: University of North Carolina - Chapel Hill
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Durham
country: United States
facility: Duke University Medical Center
state: North Carolina
city: Morgantown
country: United States
facility: West Virginia University
state: West Virginia
Study officials:
affiliation: Duke University
name: Scott Schulman, MD
role: PRINCIPAL_INVESTIGATOR
affiliation: Stanford University
name: Greg Hammer, MD
role: PRINCIPAL_INVESTIGATOR
References: