Acute Respiratory FailureNCT01938079
Pharmacokinetic Alterations During ECMO
A study testing Ketamine and Sedative drug regimen in people with Acute Respiratory Failure, run by Columbia University at 1 site in United States.
Trial summary
In a healthy patient, the lungs provide oxygen to the blood and remove carbon dioxide. However, in patients with severe lung failure, blood may not adequately be delivered to the lungs, or the lungs may not adequately supply blood with oxygen. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Acute Respiratory Failure
- What is being tested?
- Ketamine and Sedative drug regimen
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteUnited States
- Study dates
- Sep 2013to Aug 2015
- Phase
- Interventional
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Receiving ECMO for acute respiratory failure
- Requiring deep sedation (RASS -5)
Who cannot join
- Allergy to ketamine
Trial locations and contacts
1 site in 1 country.
United States1 site
NewYork-Presbyterian Hospital
New York, New York, 10032
About this study
Official title: Pharmacokinetic Alterations During ECMO (Ketamine and Extracorporeal Membrane Oxygenation)
In a healthy patient, the lungs provide oxygen to the blood and remove carbon dioxide. However, in patients with severe lung failure, blood may not adequately be delivered to the lungs, or the lungs may not adequately supply blood with oxygen. In this case, patients may require assistance from a machine to help provide this oxygen. Extracorporeal membrane oxygenation (ECMO) is a device that acts as an artificial lung, allowing the patient to recover from their illness. Patients receiving support from ECMO are often put in a medically induced coma while their lungs heal. Certain drugs may stick to the internal surfaces of the machine; therefore leading to decreased concentrations. Patients receiving ECMO often require high doses of both pain medications and sedatives in order to provide comfort. Low doses of a drug, ketamine, may help to provide additive effects to pain relief and allow lower doses of other pain medications. The hypothesis is that patients treated with continuous intravenous ketamine, will have lower requirements of other pain medications while receiving ECMO for acute respiratory failure while achieving the desired level of sedation.
Read the detailed description
The administration of analgesia and sedation is common practice for patients receiving mechanical ventilation with extracorporeal membrane oxygenation (ECMO). Maintaining patient comfort and safety, while not oversedating and thereby risking prolonged mechanical ventilation and delirium, is an ongoing balancing act which presents a daily challenge for Intensive Care Unit (ICU) clinicians. Medication selection should be based on the patient's needs with titration to a predetermined goal in accordance with published guidelines.
However, there are major pharmacokinetic changes that occur with the use of ECMO, including sequestration of medications within the circuit, increased volume of distribution, and in some cases decreased clearance. As a result patient's receiving ECMO often require very high doses of both analgesics and sedatives in order to provide comfort and ventilator synchrony. In patients not receiving ECMO, excess sedative exposure, especially with benzodiazepines, leads to increased mechanical ventilation time, prolonged ICU stay, short and long term neurocognitive impairments, and increased mortality. No studies address these outcomes in patients receiving ECMO.
Ketamine, a non-barbiturate phencyclidine derivative, provides analgesia with relative hemodynamic stability and maintained airway reflexes. However, its popularity waned because of an undesirable side effect profile: Hallucinations, delirium, lacrimation, tachycardia, and potential for an increase in intracranial pressure (ICP) and coronary ischemia. Recent research, however, suggests that low doses of ketamine infusions in combination with opiates may not be associated with adverse sequelae and may improve outcomes in the critically ill population. To date, there are no studies that have compared clinical outcomes in ICU patients sedated with ketamine as compared with other sedative agents.
Supplemental sedation with intravenous ketamine infusion may decrease opioid and sedative requirements for patients receiving mechanical ventilation and ECMO. The benefits of decreased opioid and sedative requirements may translate to fewer gastrointestinal side effects, decreased withdrawal syndromes, and a reduced rate of delirium.
Deep levels of sedation are often required at the commencement of ECMO for acute respiratory failure, which correlates to a Richmond Agitation Sedation Score (RASS) of -5. Supplemental low doses of ketamine infusions may help the prescriber achieve this goal without having to use very high doses of fentanyl or hydromorphone and midazolam.
- Conditions
- Acute Respiratory Failure
- Being tested
- Ketamine, Sedative drug regimen
- Keywords
- ECMO, Ketamine, Opiates, Lung failure, Extracorporeal membrane oxygenation, Mechanical ventilation, Sedation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
KetamineDrug
Also called Ketalar
Ketamine will be initiated as a one-time 40 mg bolus of ketamine followed by a continuous intravenous infusion of 5 micrograms/kg/min at the start of ECMO.
Sedative drug regimenOther
(Standard of Care) Fentanyl or hydromorphone and midazolam infusions will be administered to all patients and titrated at the discretion of the attending physician to maintain the desired level of sedation.
| Study group | Role | What they receive |
|---|---|---|
| Sedative without Ketamine | Active comparator | Subjects will receive sedative drug regimen without Ketamine. Receives: Other: Sedative drug regimen |
| Sedative with Ketamine | Experimental | Subjects will receive sedative drug regimen with Ketamine. Receives: Drug: Ketamine; Other: Sedative drug regimen |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative Fentanyl Equivalents From ECMO Initiation to Decision to Achieve Wakefulness
Culmulative fentanyl equivalents meaning the combination of sedative drug regimen - measured in mg - from ECMO initiation to decision to achieve wakefulness.
Measured: Up to 14 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Sep 2013 (estimated)
- Study startSep 2013
- Primary completionFeb 2015
- Study completionAug 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Other trials for Acute Respiratory FailureStudies of the same condition, open and under way.
- More trials run by Columbia UniversityThe sponsor's other registered studies.
- 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 N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Columbia University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Daniel Brodie, Columbia University
- Investigators
- Daniel Brodie, MD, Principal investigator, Columbia University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01938079
- Sponsor's protocol ID
- AAAM0950
- Status last verified
- Aug 2016
- First submitted
- 5 Sep 2013
- Last updated
- 29 Sep 2016
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 29 Sep 2016. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Pharmacokinetic Alterations During ECMO (Ketamine and Extracorporeal Membrane Oxygenation)
- ClinicalTrials.gov ID
- NCT01938079
- Acronym / sponsor ID
- AAAM0950
- Conditions
- Acute Respiratory Failure
- Keywords
- ECMO, Ketamine, Opiates, Lung failure, Extracorporeal membrane oxygenation, Mechanical ventilation, Sedation
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Columbia UniversityUniversity, hospital or other
- Study start
- Sep 2013
- Primary completion
- Feb 2015 (actual)
- Study completion
- Aug 2015 (actual)
- First posted
- 10 Sep 2013 (estimated)
- Results
- Posted 29 Sep 2016
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
In a healthy patient, the lungs provide oxygen to the blood and remove carbon dioxide. However, in patients with severe lung failure, blood may not adequately be delivered to the lungs, or the lungs may not adequately supply blood with oxygen. In this case, patients may require assistance from a machine to help provide this oxygen. Extracorporeal membrane oxygenation (ECMO) is a device that acts as an artificial lung, allowing the patient to recover from their illness. Patients receiving support from ECMO are often put in a medically induced coma while their lungs heal. Certain drugs may stick to the internal surfaces of the machine; therefore leading to decreased concentrations. Patients receiving ECMO often require high doses of both pain medications and sedatives in order to provide comfort. Low doses of a drug, ketamine, may help to provide additive effects to pain relief and allow lower doses of other pain medications. The hypothesis is that patients treated with continuous intravenous ketamine, will have lower requirements of other pain medications while receiving ECMO for acute respiratory failure while achieving the desired level of sedation.
Detailed description
The administration of analgesia and sedation is common practice for patients receiving mechanical ventilation with extracorporeal membrane oxygenation (ECMO). Maintaining patient comfort and safety, while not oversedating and thereby risking prolonged mechanical ventilation and delirium, is an ongoing balancing act which presents a daily challenge for Intensive Care Unit (ICU) clinicians. Medication selection should be based on the patient's needs with titration to a predetermined goal in accordance with published guidelines.
However, there are major pharmacokinetic changes that occur with the use of ECMO, including sequestration of medications within the circuit, increased volume of distribution, and in some cases decreased clearance. As a result patient's receiving ECMO often require very high doses of both analgesics and sedatives in order to provide comfort and ventilator synchrony. In patients not receiving ECMO, excess sedative exposure, especially with benzodiazepines, leads to increased mechanical ventilation time, prolonged ICU stay, short and long term neurocognitive impairments, and increased mortality. No studies address these outcomes in patients receiving ECMO.
Ketamine, a non-barbiturate phencyclidine derivative, provides analgesia with relative hemodynamic stability and maintained airway reflexes. However, its popularity waned because of an undesirable side effect profile: Hallucinations, delirium, lacrimation, tachycardia, and potential for an increase in intracranial pressure (ICP) and coronary ischemia. Recent research, however, suggests that low doses of ketamine infusions in combination with opiates may not be associated with adverse sequelae and may improve outcomes in the critically ill population. To date, there are no studies that have compared clinical outcomes in ICU patients sedated with ketamine as compared with other sedative agents.
Supplemental sedation with intravenous ketamine infusion may decrease opioid and sedative requirements for patients receiving mechanical ventilation and ECMO. The benefits of decreased opioid and sedative requirements may translate to fewer gastrointestinal side effects, decreased withdrawal syndromes, and a reduced rate of delirium.
Deep levels of sedation are often required at the commencement of ECMO for acute respiratory failure, which correlates to a Richmond Agitation Sedation Score (RASS) of -5. Supplemental low doses of ketamine infusions may help the prescriber achieve this goal without having to use very high doses of fentanyl or hydromorphone and midazolam.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Sedative without Ketamine | Active comparator | Other: Sedative drug regimenSubjects will receive sedative drug regimen without Ketamine. |
| Sedative with Ketamine | Experimental | Drug: Ketamine, Other: Sedative drug regimenSubjects will receive sedative drug regimen with Ketamine. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Receiving ECMO for acute respiratory failure
- Requiring deep sedation (RASS -5)
Key exclusion criteria (1 listed)
- Allergy to ketamine
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 |
|---|---|---|
| KetamineAlso: KetalarKetamine will be initiated as a one-time 40 mg bolus of ketamine followed by a continuous intravenous infusion of 5 micrograms/kg/min at the start of ECMO. | Drug | Sedative with Ketamine |
| Sedative drug regimen(Standard of Care) Fentanyl or hydromorphone and midazolam infusions will be administered to all patients and titrated at the discretion of the attending physician to maintain the desired level of sedation. | Other | Sedative with Ketamine, Sedative without Ketamine |
Primary outcome
Cumulative Fentanyl Equivalents From ECMO Initiation to Decision to Achieve Wakefulness
Time frame: Up to 14 days
Culmulative fentanyl equivalents meaning the combination of sedative drug regimen - measured in mg - from ECMO initiation to decision to achieve wakefulness.
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 29 Sep 2016.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Individual participant dataSharing planned: No
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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.
Daniel Brodie, MD principal investigator
Columbia University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Ketamine and Sedative drug regimen in people with Acute Respiratory Failure, run by Columbia University at 1 site in United States.
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 2 inclusion and 1 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: finished, as of the sponsor's last update on 29 Sep 2016. 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 United States. 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.
Are results available for this study?
Yes. Results are posted in the registry (first posted 29 Sep 2016). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Cumulative Fentanyl Equivalents From ECMO Initiation to Decision to Achieve Wakefulness (time frame: Up to 14 days). 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 29 Sep 2016.