Sodium Nitroprusside for Blood Pressure Reduction in the ICU (SNP2)

Study Overview
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Brief Summary
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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
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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.

Official Title
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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

Conditions
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Hypertension

Intervention / Treatment
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* Drug: nitroprusside
* Drug: placebo infusion


Participation Criteria
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Eligibility Criteria
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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.

Ages Eligible for Study
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Minimum Age: 1 Day
Maximum Age: 17 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Single Group Assignment
Masking: Triple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Active Comparator: 1<br>Blinded nitroprusside infusion | Drug: nitroprusside<br>* nitroprusside continuous infusion, dose to be titrated to clinical effect<br>* Other names: Nipride;|
| Placebo Comparator: 2<br>Blinded placebo infusion | Drug: placebo infusion<br>* blinded placebo infusion, to be infused at same rate as open-label nitroprusside infusion<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| The primary endpoint is the change in MAP during the Blinded Study Drug Administration Phase in the absence of other stimuli. |  | 8 months | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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. |  | 8 months | 
| 2. To compare the proportion of patients randomized to receive either sodium nitroprusside or placebo who experience rebound hypertension during blinded study drug period |  | 8 months | 
| 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 |  | 8 months | 
| 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. |  | 8 months | 
| 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 |  | 8 months | 
| 6. To compare the changes in individual laboratory parameters between patients randomized to receive either sodium nitroprusside or placebo. |  | 8 months | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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nitroprusside, intensive care unit, hypertension, blood pressure reduction