Safety Study of Nebulized Sodium Nitroprusside in Adult Acute Lung Injury

NCT01619280 | Unknown Phase 1

• 1 other identifier: 10-0102-A
• Study Type: interventional
• Target: 30
• Locations: 1 country
• Sites: 1

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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.

  Up to 1 year

Secondary Outcomes (3)

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

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

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

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

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

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

Study Arms (1)

Nebulized sodium nitroprusside

EXPERIMENTAL

Drug: Sodium Nitroprusside

Interventions

Sodium Nitroprusside DRUG

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.

Also known as: Nipride, Nitropress

Nebulized sodium nitroprusside

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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

You may not qualify if:

• 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.

Sponsors & Collaborators

• Mount Sinai Hospital, Canada: lead

Study Sites (1)

Mount Sinai Hospital, University of Toronto

Toronto, Ontario, M5G 1X5, Canada

RECRUITING

MeSH Terms

Conditions

Acute Lung Injury; Respiratory Distress Syndrome; Hypoxia; Respiratory Insufficiency; Lung Injury

Interventions

Nitroprusside

Condition Hierarchy (Ancestors)

Lung Diseases; Respiratory Tract Diseases; Respiration Disorders; Signs and Symptoms, Respiratory; Signs and Symptoms; Pathological Conditions, Signs and Symptoms; Thoracic Injuries; Wounds and Injuries

Intervention Hierarchy (Ancestors)

Ferricyanides; Cyanides; Anions; Ions; Electrolytes; Inorganic Chemicals; Ferric Compounds; Iron Compounds; Hydrogen Cyanide; Nitrogen Compounds

Study Officials

• Sangeeta Mehta, MD FRCPC

  Department of Critical Care Medicine, University of Toronto

  PRINCIPAL INVESTIGATOR

• Terence Ip, MD

  Department of Critical Care Medicine, University of Toronto

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Terence Ip, MD

CONTACT

terence.ip@utoronto.ca

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 29, 2012
• First Posted: June 14, 2012
• Study Start: May 1, 2012
• Primary Completion: June 1, 2013
• Study Completion: June 1, 2013
• Last Updated: June 14, 2012

Record last verified: 2012-06

Locations

CA (1)