Safety Study of Nebulized Sodium Nitroprusside in Adult Acute Lung Injury
Information source: Mount Sinai Hospital, Canada
ClinicalTrials.gov processed this data on August 23, 2015 Link to the current ClinicalTrials.gov record.
Condition(s) targeted: Acute Lung Injury; Acute Respiratory Distress Syndrome; Sodium Nitroprusside; Hypoxia; Respiratory Failure
Intervention: Sodium Nitroprusside (Drug)
Phase: Phase 1
Status: Recruiting
Sponsored by: Mount Sinai Hospital, Canada Official(s) and/or principal investigator(s): Sangeeta Mehta, MD FRCPC, Principal Investigator, Affiliation: Department of Critical Care Medicine, University of Toronto Terence Ip, MD, Principal Investigator, Affiliation: Department of Critical Care Medicine, University of Toronto
Overall contact: Terence Ip, MD, Email: terence.ip@utoronto.ca
Summary
Acute lung injury (ALI) is caused by a wide variety of conditions, but always characterized
by hypoxia and non-cardiogenic pulmonary edema. Current treatment of ALI is supportive and
treatment of the underlying cause. New therapies to treat severe ALI have not been shown to
improve survival, and are limited by financial and logistical resources.
The investigators propose to investigate the role of inhaled sodium nitroprusside (iSNP) in
ALI. Sodium nitroprusside (SNP) is a vasodilator. When inhaled, SNP may travel to areas of
the lung participating in gas exchange, and cause the blood vessels surrounding these areas
to enlarge. This may result in an increase of blood vessels to these areas of the lung, and
improve oxygenation. Currently, iSNP has not been studied in the adult population.
Therefore, this study is intended to find the safety profile of varying doses of iSNP.
Clinical Details
Official title: A Phase 1 Study: The Determination of the Maximum Tolerable Dosage of Nebulized Sodium Nitroprusside in Adult Acute Lung Injury
Study design: Endpoint Classification: Safety/Efficacy Study, Intervention Model: Single Group Assignment, Masking: Open Label, Primary Purpose: Treatment
Primary outcome: The maximum tolerable dosage of nebulized sodium nitroprusside. This will be determined by the 3 + 3 dose finding design.
Secondary outcome: The change in measures of oxygenation (PaO2,SaO2,oxygenation index) during iSNP administration.The change in heart rate (HR), mean blood pressure (MAP) during iSNP administration. The presence or absence of lactate, and/or methemoglobin.
Detailed description:
Acute lung injury (ALI) is a syndrome characterized by acute hypoxemic respiratory failure
with bilateral pulmonary infiltrates that are not attributed to left atrial hypertension.
ALI is responsible for significant mortality and morbidity in the critically ill population.
Novel rescue therapies used to support oxygenation in severe ALI include inhaled nitric
oxide and high frequency oscillatory ventilation; however, neither have been shown to reduce
mortality and both are limited by logistical and financial challenges.
Inhaled sodium nitroprusside (iSNP) is a vasodilator which causes local vasodilation of
pulmonary capillaries surrounding functional alveoli, resulting in improved oxygenation by
redistributing pulmonary blood flow to areas with better ventilation-perfusion ratios. As
iSNP can be administered by a low-cost nebulizer and is relatively inexpensive compared to
other novel rescue therapies, this modality may be an alternative therapy for patients with
severe hypoxemia. Two pediatric studies support the use of iSNP in ALI; however, iSNP has
not been studied in the adult ALI population. To determine whether iSNP can improve
oxygenation in adult ALI, the maximum tolerable dose (MTD) must first be determined.
Our study aims to determine the MTD of iSNP in adult ALI through an open-label,
non-randomized, single centered, dose escalation study design, whereby subjects will receive
iSNP for thirty minutes and have various physiologic variables recorded.
Eligibility
Minimum age: 18 Years.
Maximum age: N/A.
Gender(s): Both.
Criteria:
Inclusion Criteria:
1. Age ≥ 18
2. Negative β-hCG in women of child bearing age (age ≤ 50)
3. Developed ALI within past 72 hours:
- PaO2/FiO2 < 300;
- Bilateral infiltrates on CXR;
- No clinical evidence of elevated left atrial pressure ie. Heart failure as the
cause of hypoxia and bilateral infiltrates; and
- Recognized risk factor for ALI such as: pneumonia, aspiration pneumonitis, acute
pancreatitis, massive blood transfusion, or sepsis
4. FiO2 ≥ 0. 5
5. PEEP ≥ 8 cm H2O
6. Invasive arterial blood pressure line
7. Endotracheal intubation or tracheostomy
8. Conventional mechanical ventilation
9. Mean Arterial Pressure (MAP) ≥ 65 mmHg with or without use of vasopressors (stable
for at least more than 1 hour)
10. Arterial pH ≥ 7. 15
Exclusion Criteria:
1. Chest tube with active leak (eg. bronchopulmonary fistula),
2. Prone ventilation, inhaled nitric oxide, inhaled prostacyclin, high frequency
oscillatory ventilation,
3. Lack of consent,
4. Untreated coarctation of aorta, symptomatic or severe/critical aortic stenosis as
documented by echocardiogram or clinical history,
5. Evidence of increased intracranial pressure (eg. dilated pupils, known intracranial
trauma or mass on head CT),
6. SpO2 <90%,
7. Contraindication to SNP i. e. hypersensitivity, congenital optic atrophy, tobacco
amblyopia,
8. Active treatment with IV or transdermal nitroglycerin,
9. G6PD deficiency
10. CrCl < 30 ml/min or receiving renal replacement therapy, or
11. Total bilirubin > 68 µmol/L and AST or ALT level 2 times the upper limit of normal.
Locations and Contacts
Terence Ip, MD, Email: terence.ip@utoronto.ca
Mount Sinai Hospital, University of Toronto, Toronto, Ontario M5G 1X5, Canada; Recruiting Terence Ip, MD, Principal Investigator Sangeeta Mehta, MD FRCPC, Principal Investigator Lisa Burry, PharmD, Sub-Investigator Cynthia Harris, RRT, Sub-Investigator John Traill, RRT, Sub-Investigator Niall Ferguson, MD, FRCPC, Sub-Investigator
Additional Information
Starting date: May 2012
Last updated: June 12, 2012
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