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Safety Study of Nebulized Sodium Nitroprusside in Adult Acute Lung Injury

Primary Purpose

Acute Lung Injury, Acute Respiratory Distress Syndrome, Sodium Nitroprusside

Status

Unknown status

Phase

Phase 1

Locations

Canada

Study Type

Interventional

Intervention

Sodium Nitroprusside

About this trial

This is an interventional treatment trial for Acute Lung Injury focused on measuring Acute Lung Injury, Acute Respiratory Distress Syndrome, Sodium Nitroprusside, adult, Safety, Dose Finding, Phase 1, 3 + 3 design, Nebulizers and Vaporizers, High-Frequency Ventilation, nitric oxide, lung injury, Pulmonary Gas Exchange, Pulmonary Alveoli

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

Age ≥ 18
Negative β-hCG in women of child bearing age (age ≤ 50)
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
FiO2 ≥ 0.5
PEEP ≥ 8 cm H2O
Invasive arterial blood pressure line
Endotracheal intubation or tracheostomy
Conventional mechanical ventilation
Mean Arterial Pressure (MAP) ≥ 65 mmHg with or without use of vasopressors (stable for at least more than 1 hour)
Arterial pH ≥ 7.15

Exclusion Criteria:

Chest tube with active leak (eg. bronchopulmonary fistula),
Prone ventilation, inhaled nitric oxide, inhaled prostacyclin, high frequency oscillatory ventilation,
Lack of consent,
Untreated coarctation of aorta, symptomatic or severe/critical aortic stenosis as documented by echocardiogram or clinical history,
Evidence of increased intracranial pressure (eg. dilated pupils, known intracranial trauma or mass on head CT),
SpO2 <90%,
Contraindication to SNP i.e. hypersensitivity, congenital optic atrophy, tobacco amblyopia,
Active treatment with IV or transdermal nitroglycerin,
G6PD deficiency
CrCl < 30 ml/min or receiving renal replacement therapy, or
Total bilirubin > 68 µmol/L and AST or ALT level 2 times the upper limit of normal.

Sites / Locations

Mount Sinai Hospital, University of TorontoRecruiting

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Nebulized sodium nitroprusside

Arm Description

Outcomes

Primary Outcome Measures

The maximum tolerable dosage of nebulized sodium nitroprusside. This will be determined by the 3 + 3 dose finding design.

Participants will be followed for the duration of the intervention of 45 min. . It is anticipated it will take up to 1 year to recruit the required number of participants to determine the maximum tolerable dose of nebulized sodium nitroprusside.

Secondary Outcome Measures

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.

Full Information

NCT ID

NCT01619280

First Posted

May 29, 2012

Last Updated

June 12, 2012

Sponsor

Mount Sinai Hospital, Canada

1. Study Identification

Unique Protocol Identification Number

NCT01619280

Brief Title

Safety Study of Nebulized Sodium Nitroprusside in Adult Acute Lung Injury

Official Title

A Phase 1 Study: The Determination of the Maximum Tolerable Dosage of Nebulized Sodium Nitroprusside in Adult Acute Lung Injury

Study Type

Interventional

2. Study Status

Record Verification Date

June 2012

Overall Recruitment Status

Unknown status

Study Start Date

May 2012 (undefined)

Primary Completion Date

June 2013 (Anticipated)

Study Completion Date

June 2013 (Anticipated)

3. Sponsor/Collaborators

Responsible Party, by Official Title

Sponsor

Name of the Sponsor

Mount Sinai Hospital, Canada

4. Oversight

Data Monitoring Committee

5. Study Description

Brief 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.

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.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study

Acute Lung Injury, Acute Respiratory Distress Syndrome, Sodium Nitroprusside, Hypoxia, Respiratory Failure

Keywords

Acute Lung Injury, Acute Respiratory Distress Syndrome, Sodium Nitroprusside, adult, Safety, Dose Finding, Phase 1, 3 + 3 design, Nebulizers and Vaporizers, High-Frequency Ventilation, nitric oxide, lung injury, Pulmonary Gas Exchange, Pulmonary Alveoli

7. Study Design

Primary Purpose

Treatment

Study Phase

Phase 1

Interventional Study Model

Single Group Assignment

Masking

None (Open Label)

Allocation

N/A

Enrollment

30 (Anticipated)

8. Arms, Groups, and Interventions

Arm Title

Nebulized sodium nitroprusside

Arm Type

Experimental

Intervention Type

Drug

Intervention Name(s)

Sodium Nitroprusside

Other Intervention Name(s)

Nipride, Nitropress

Intervention Description

Each subject will receive one of five possible dosages of nebulized sodium nitroprusside. The dosage will be determined by the 3 + 3 dose escalation design. Only a maximum of six patients will be given a particular dosage. Arterial blood gases will be drawn at 0 min, 15 min, 30 min and 45 min during nebulized sodium nitroprusside administration. Vitals signs will be recorded every five minutes. No changes to ventilator settings or vasopressor dosage or fluid administration will be allowed.

Primary Outcome Measure Information:

Title

The maximum tolerable dosage of nebulized sodium nitroprusside. This will be determined by the 3 + 3 dose finding design.

Description

Time Frame

Up to 1 year

Secondary Outcome Measure Information:

Title

The change in measures of oxygenation (PaO2,SaO2,oxygenation index) during iSNP administration.

Time Frame

0 min, 15 min, 30 min, and 45 min

Title

The change in heart rate (HR), mean blood pressure (MAP) during iSNP administration.

Time Frame

0 min, 15 min, 30 min, and 45 min

Title

The presence or absence of lactate, and/or methemoglobin.

Time Frame

0 min, 15 min, 30 min, and 45 min

10. Eligibility

Sex

All

Minimum Age & Unit of Time

18 Years

Accepts Healthy Volunteers

Eligibility Criteria

Inclusion Criteria: Age ≥ 18 Negative β-hCG in women of child bearing age (age ≤ 50) 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 FiO2 ≥ 0.5 PEEP ≥ 8 cm H2O Invasive arterial blood pressure line Endotracheal intubation or tracheostomy Conventional mechanical ventilation Mean Arterial Pressure (MAP) ≥ 65 mmHg with or without use of vasopressors (stable for at least more than 1 hour) Arterial pH ≥ 7.15 Exclusion Criteria: Chest tube with active leak (eg. bronchopulmonary fistula), Prone ventilation, inhaled nitric oxide, inhaled prostacyclin, high frequency oscillatory ventilation, Lack of consent, Untreated coarctation of aorta, symptomatic or severe/critical aortic stenosis as documented by echocardiogram or clinical history, Evidence of increased intracranial pressure (eg. dilated pupils, known intracranial trauma or mass on head CT), SpO2 <90%, Contraindication to SNP i.e. hypersensitivity, congenital optic atrophy, tobacco amblyopia, Active treatment with IV or transdermal nitroglycerin, G6PD deficiency CrCl < 30 ml/min or receiving renal replacement therapy, or Total bilirubin > 68 µmol/L and AST or ALT level 2 times the upper limit of normal.

Central Contact Person:

First Name & Middle Initial & Last Name or Official Title & Degree

Terence Ip, MD

terence.ip@utoronto.ca

Overall Study Officials:

First Name & Middle Initial & Last Name & Degree

Sangeeta Mehta, MD FRCPC

Organizational Affiliation

Department of Critical Care Medicine, University of Toronto

Official's Role

Principal Investigator

First Name & Middle Initial & Last Name & Degree

Terence Ip, MD

Organizational Affiliation

Department of Critical Care Medicine, University of Toronto

Official's Role

Principal Investigator

Facility Information:

Facility Name

Mount Sinai Hospital, University of Toronto

City

Toronto

State/Province

Ontario

ZIP/Postal Code

M5G 1X5

Country

Canada

Individual Site Status

Recruiting

Facility Contact:

First Name & Middle Initial & Last Name & Degree

Terence Ip, MD

First Name & Middle Initial & Last Name & Degree

Sangeeta Mehta, MD FRCPC

First Name & Middle Initial & Last Name & Degree

Lisa Burry, PharmD

First Name & Middle Initial & Last Name & Degree

Cynthia Harris, RRT

First Name & Middle Initial & Last Name & Degree

John Traill, RRT

First Name & Middle Initial & Last Name & Degree

Niall Ferguson, MD, FRCPC

12. IPD Sharing Statement

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Safety Study of Nebulized Sodium Nitroprusside in Adult Acute Lung Injury

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