Acute Lung InjuryPhase 1NCT01619280
Safety Study of Nebulized Sodium Nitroprusside in Adult Acute Lung Injury
A Phase 1 study testing Sodium Nitroprusside in people with Acute Lung Injury and Acute Respiratory Distress Syndrome, run by Mount Sinai Hospital, Canada at 1 site in Canada.
Trial 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. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Lung Injury, Acute Respiratory Distress Syndrome, Sodium Nitroprusside
- What is being tested?
- Sodium Nitroprusside
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 30 participants
- Where
- 1 siteCanada
- Study dates
- May 2012to Jun 2013
- Phase
- Phase 1
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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
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- 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
Who cannot join
- 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%,
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- 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.
Trial locations and contacts
1 site in 1 country.
Terence Ip, MD contact
Canada1 site, 1 recruiting
- Recruiting
Mount Sinai Hospital, University of Toronto
Toronto, Ontario, M5G 1X5
Terence Ip, MD
Sangeeta Mehta, MD FRCPC
About this study
Official title: 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.
Read the 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.
- Conditions
- Acute Lung Injury, Acute Respiratory Distress Syndrome, Sodium Nitroprusside, Hypoxia, Respiratory Failure
- Being tested
- Sodium Nitroprusside
- 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
- Medical subject headings
- Acute Lung Injury, Respiratory Distress Syndrome, Hypoxia, Respiratory Insufficiency, Lung Injury
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Sodium NitroprussideDrug
Also called Nipride, Nitropress
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.
| Study group | Role | What they receive |
|---|---|---|
| Nebulized sodium nitroprusside | Experimental | Not described Receives: Drug: Sodium Nitroprusside |
What is being measured
The primary outcome is the main question the study is designed to answer.
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.
Measured: Up to 1 year
Secondary outcomes (3)
The change in measures of oxygenation (PaO2,SaO2,oxygenation index) during iSNP administration.
Measured: 0 min, 15 min, 30 min, and 45 min
The change in heart rate (HR), mean blood pressure (MAP) during iSNP administration.
Measured: 0 min, 15 min, 30 min, and 45 min
The presence or absence of lactate, and/or methemoglobin.
Measured: 0 min, 15 min, 30 min, and 45 min
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Jun 2012 (estimated)
- Study startMay 2012
- Primary completionJun 2013 (estimated)
- Study completionJun 2013 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Acute Lung InjuryStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 30 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Mount Sinai Hospital, Canada
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Sangeeta Mehta, MD FRCPC, Principal investigator, Department of Critical Care Medicine, University of TorontoTerence Ip, MD, Principal investigator, Department of Critical Care Medicine, University of Toronto
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01619280
- Sponsor's protocol ID
- 10-0102-A
- Status last verified
- Jun 2012
- First submitted
- 29 May 2012
- Last updated
- 14 Jun 2012
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 14 Jun 2012. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Phase 1 Study: The Determination of the Maximum Tolerable Dosage of Nebulized Sodium Nitroprusside in Adult Acute Lung Injury
- ClinicalTrials.gov ID
- NCT01619280
- Acronym / sponsor ID
- 10-0102-A
- 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
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 30 participants (estimated)
- Lead sponsor
- Mount Sinai Hospital, CanadaUniversity, hospital or other
- Study start
- May 2012
- Primary completion
- Jun 2013 (estimated)
- Study completion
- Jun 2013 (estimated)
- First posted
- 14 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Nebulized sodium nitroprusside | Experimental | Drug: Sodium Nitroprusside |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (14 listed)
- Age ≥ 18
- Negative β-hCG in women of child bearing age (age ≤ 50)
- Developed ALI within past 72 hours:
- FiO2 ≥ 0.5
- PEEP ≥ 8 cm H2O
Key exclusion criteria (11 listed)
- 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),
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Sodium NitroprussideAlso: Nipride, NitropressEach 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. | Drug | Nebulized sodium nitroprusside |
Primary outcome
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
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.
3 secondary outcomes
The change in measures of oxygenation (PaO2,SaO2,oxygenation index) during iSNP administration.
Time frame: 0 min, 15 min, 30 min, and 45 min
The change in heart rate (HR), mean blood pressure (MAP) during iSNP administration.
Time frame: 0 min, 15 min, 30 min, and 45 min
The presence or absence of lactate, and/or methemoglobin.
Time frame: 0 min, 15 min, 30 min, and 45 min
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Jun 2012.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Terence Ip, MD contact
Sangeeta Mehta, MD FRCPC principal investigator
Department of Critical Care Medicine, University of Toronto
Terence Ip, MD principal investigator
Department of Critical Care Medicine, University of Toronto
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing Sodium Nitroprusside in people with Acute Lung Injury and Acute Respiratory Distress Syndrome, run by Mount Sinai Hospital, Canada at 1 site in Canada.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 14 inclusion and 11 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 14 Jun 2012. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Canada. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Terence Ip, MD (terence.ip@utoronto.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the 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). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 14 Jun 2012.