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Safety Study of Nebulized Sodium Nitroprusside in Adult Acute Lung Injury

The recruitment status of this study is unknown because the information has not been verified recently.
Verified June 2012 by Mount Sinai Hospital, Canada.
Recruitment status was  Recruiting
Sponsor:
Information provided by (Responsible Party):
Mount Sinai Hospital, Canada
ClinicalTrials.gov Identifier:
NCT01619280
First received: May 29, 2012
Last updated: June 12, 2012
Last verified: June 2012

May 29, 2012
June 12, 2012
May 2012
June 2013   (final data collection date for primary outcome measure)
The maximum tolerable dosage of nebulized sodium nitroprusside. This will be determined by the 3 + 3 dose finding design. [ Time Frame: Up to 1 year ] [ Designated as safety issue: Yes ]
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.
Same as current
Complete list of historical versions of study NCT01619280 on ClinicalTrials.gov Archive Site
  • The change in measures of oxygenation (PaO2,SaO2,oxygenation index) during iSNP administration. [ Time Frame: 0 min, 15 min, 30 min, and 45 min ] [ Designated as safety issue: No ]
  • The change in heart rate (HR), mean blood pressure (MAP) during iSNP administration. [ Time Frame: 0 min, 15 min, 30 min, and 45 min ] [ Designated as safety issue: Yes ]
  • The presence or absence of lactate, and/or methemoglobin. [ Time Frame: 0 min, 15 min, 30 min, and 45 min ] [ Designated as safety issue: Yes ]
Same as current
Not Provided
Not Provided
 
Safety Study of Nebulized Sodium Nitroprusside in Adult Acute Lung Injury
A Phase 1 Study: The Determination of the Maximum Tolerable Dosage of Nebulized Sodium Nitroprusside in Adult Acute Lung Injury

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.

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.

Interventional
Phase 1
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
  • Acute Lung Injury
  • Acute Respiratory Distress Syndrome
  • Sodium Nitroprusside
  • Hypoxia
  • Respiratory Failure
Drug: Sodium Nitroprusside
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.
Other Name: Nipride, Nitropress
Experimental: Nebulized sodium nitroprusside
Intervention: Drug: Sodium Nitroprusside
Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruiting
30
June 2013
June 2013   (final data collection date for primary outcome measure)

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.
Both
18 Years and older
No
Contact: Terence Ip, MD terence.ip@utoronto.ca
Canada
 
NCT01619280
10-0102-A
No
Mount Sinai Hospital, Canada
Mount Sinai Hospital, Canada
Not Provided
Principal Investigator: 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
Mount Sinai Hospital, Canada
June 2012

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP