Postcardiac Arrest Therapeutic HypothermiaNCT02033733
When Cooling a Patient After Cardiac Arrest, Does Use of a Neuromuscular Blocking Agent Make Your Job Easier?
An observational study of Postcardiac Arrest Therapeutic Hypothermia, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 2 sites in Canada.
Trial summary
After successful resuscitation from cardiac arrest, cooling the whole body is a well established treatment that improves the chances of the brain recovering. This however, has to be done within a certain time-frame from the arrest. Read more about this study
- Who is it for?
- Ages 18 to 90 years
- Conditions the study is for
- Postcardiac Arrest Therapeutic Hypothermia
- What is being tested?
- Cisatracurium infusion and Cisatracurium prn bolus
- Type of treatment
- Injection or infusion
- How many people
- 400 participants
- Where
- 2 sitesCanada
- Study dates
- Jan 2014to Feb 2015
- Phase
- Observational
- 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 to 90 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Study population: All patients admitted to the intensive care unit (ICU) with a diagnosis of postcardiac arrest between Jan 2008 and Dec 2012 will be examined.
Who may be able to join
- Admission to adult ICU (age ≥18 years) at London Health Sciences Centre
- Primary reason for ICU admission: postcardiac arrest
- Both in-hospital and out-of-hospital cardiac arrest will be included
- ICU admission between Jan 2008 and Dec 2012.
Who cannot join
- ICU admissions primarily for reasons other than cardiac arrest.
Trial locations and contacts
2 sites in 1 country.
Eyad AlThenayan, MD contact
Canada2 sites
University Hospital, London Health Sciences Centre, University of Western Ontario
London, Ontario, N6A 5A5
Ahmed F Hegazy, MD, FRCPC, 1(519) 860-4917, ahmed.hegazy@londonhospitals.ca
Eyad Althenayan, MD, 1 (519) 685-8500 ext. 19119, eyad.althenayan@lhsc.on.ca
Victoria Hospital, London Health Sciences Centre, University of Western Ontario
London, Ontario, N6A 5W9
Ahmed F Hegazy, MD, FRCPC, 1(519) 860-4917, ahmed.hegazy@londonhospitals.ca
Eyad Althenayan, MD, 1 (519) 685-8500 ext. 19119, eyad.althenayan@lhsc.on.ca
About this study
Official title: Post-arrest Therapeutic Hypothermia. Does Use of Neuromuscular Blockers Achieve Faster Cooling Time?
After successful resuscitation from cardiac arrest, cooling the whole body is a well established treatment that improves the chances of the brain recovering. This however, has to be done within a certain time-frame from the arrest. The purpose of this study is to explore the best way of dosing the muscle relaxing medications that are given during the cooling process.
Hypothesis: In the context of our institutional therapeutic hypothermia protocol, cisatracurium infusions lead to faster drops in core temperature when compared to cisatracurium prn boluses alone.
Read the detailed description
STUDY RATIONALE:
A large proportion of comatose survivors of cardiac arrest presenting to our intensive care units at London Health Sciences Centre (LHSC) undergo therapeutic hypothermia. Current evidence suggests that timely achievement of target temperatures is desirable to improve outcomes. At LHSC, this intervention is protocolized with a defined set of preprinted orders that includes a dosing regimen for neuromuscular blocking agents (NMBA's). Our preprinted protocol has been in place since January of 2004. Cisatracurium infusions were part of the therapeutic hypothermia protocol until October 2011. Since that time, our protocol has changed to cisatracurium prn boluses for any observed shivering. In this study we will examine if there has been any change in the times to achieving target temperatures with the implementation of this change. It is important to note that no other change in our protocol has taken place since it was first implemented, making our before and after comparison valid and fair.
Our hypothesis is that NMBA infusions lead to a faster drop in core temperatures when compared to NMBA prn boluses. If this were to stand true, we would expect cisatracurium IV infusions to result in faster reductions in core temperature when compared with cisatracurium prn boluses in the context of our therapeutic hypothermia protocol. Hypothermia has been known to cause a subclinical increase in muscle tone. This previously reported phenomenon has been named "microshivering". When attempting to reduce core temperatures, microshivering is likely a natural body response to try to restore body temperature back to normal. We therefore hypothesize that NMBA infusions are likely more effective at abolishing microshivering, which would be a desirable effect when trying to induce therapeutic hypothermia.
Although current American Heart Association (AHA) guidelines suggest considering the administration of NMBA's to facilitate induced hypothermia and control shivering. Their recommendation is to minimize the duration of NMBA use or if possible, avoid them altogether. After the publication of these guidelines our institutional protocol changed to prn boluses instead of the previous infusion orders. We therefore believe it is important to examine the effects of this change on our cooling protocol and potentially add to the growing body of knowledge in this field.
- Being tested
- Cisatracurium infusion, Cisatracurium prn bolus
- Keywords
- Post cardiac arrest, Postcardiac arrest therapeutic hypothermia, Therapeutic hypothermia protocol, Neuromuscular blocking agents, Muscle relaxants, Hypothermia-induced increased muscle tone, Microshivering
- Medical subject headings
- Muscle Hypotonia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Cisatracurium infusionDrug
Also called Neuromuscular blocking agent infusion, NMBA infusion, Continuous NMBA infusion, Continuous cisatracurium infusion
This group will include postcardiac arrest patients that have received a cisatracurium infusion as part of their therapeutic hypothermia protocol. It will only include patients that had their infusion started within 2 hours from protocol initiation. Patients that received an infusion as a rescue measure (beyond the first 2 hours) or did not receive and infusion at all will not be included in this group.
Most patients admitted to our ICU postcardiac arrest prior to October 2011, will likely belong to this group (the cisatracurium infusion group).
Cisatracurium prn bolusDrug
Also called neuromuscular blocking agent prn bolus, NMBA prn bolus, cisatracurium intermittent bolus, intermittent bolus administration of cisatracurium
Patients that have not received a cisatracurium infusion within the first 2 hours from protocol initiation will be in this group. These are likely to be patients admitted to our ICU after October 2011 (when the protocol change happened).
| Study group | Role | What they receive |
|---|---|---|
| Adequate cooling time | Patients that reached target temperature within 4 hours of initiation of the hypothermia protocol will be in the "adequate cooling time" group. Receives: Drug: Cisatracurium infusion; Drug: Cisatracurium prn bolus | |
| Inadequate cooling time | Patients that did not reach target temperature within 4 hours of initiation of the hypothermia protocol will be in the "inadequate cooling time" group. Receives: Drug: Cisatracurium infusion; Drug: Cisatracurium prn bolus |
What is being measured
The primary outcome is the main question the study is designed to answer.
Time to attaining target temperature (hours).
The primary outcome will be a binary outcome that is: adequate cooling time versus inadequate cooling time based on the time needed to achieve target temperatures. We will define adequate cooling time as being ≤ 4 hours from initiation of protocol to reaching target temperature. Inadequate cooling time will be requiring > 4 hours to achieve that goal. Target core body temperature range in our institutional protocol is 32 - 34ºC.
The primary outcome will be assessed using a logistic regression model, constructed using covariates affecting speed of cooling as determined by expert opinion and current evidence apriori. The variables will be age, sex, weight, pre-protocol core body temperature, initial arrest rhythm and infusion versus boluses. The model will be used to determine whether the cisatracurium dosing regimen is an independent predictor of adequate patient cooling time or not.
Measured: From initiation of hypothermia protocol to reaching a core body temperature of ≤34ºC, assessed up to 72 hours from protocol initiation.
Secondary outcomes (3)
Cerebral performance category score on hospital discharge.
Neurological outcome on discharge from hospital as defined by the cerebral performance category (CPC) scale. The CPC scale is a 5 point scale. The outcome measure will be dichotomized into good or bad. Good outcome will be equivalent to CPC scores of 1 \& 2 (where the patient is independent), and bad outcome will be equivalent to CPC scores of 3, 4 \& 5 (where the patient is either dependent or dead). We will examine whether the use of a neuromuscular blocking agent infusion correlates with good CPC scores on hospital discharge or not.
CPC Scale:
- Functioning normally and independent, possibly with a minor disability.
- Moderately disabled, still independent.
- Conscious but with a severe disability, dependent.
- Unconscious (comatose or in a persistent vegetative state).
- Brain dead or dead by traditional criteria.
Measured: Upon discharge from hospital, assessed up to 36 months postcardiac arrest.
Hospital length of stay postcardiac arrest (days).
Hospital length of stay (LOS) post-cardiac arrest will be calculated from the day of the cardiac arrest to the day of hospital discharge. If prior to the arrest the patient was an inpatient, we will only count the days from the arrest to discharge. Days spent in hospital prior to the arrest will not be included.
Measured: Days spent in hospital after successful resuscitation from cardiac arrest, assessed up to 36 months from the date of cardiac arrest
Intensive care unit length of stay postcardiac arrest (days).
The length of stay (LOS) in the intensive care unit (ICU) after successful resuscitation from cardiac arrest in days.
Measured: Days spent in the intensive care unit after successful resuscitation from cardiac arrest, assessed up to 36 months from the date of cardiac arrest.
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted13 Jan 2014 (estimated)
- Study startJan 2014
- Primary completionDec 2014 (estimated)
- Study completionFeb 2015 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Postcardiac Arrest Therapeutic HypothermiaStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Retrospective
- Enrolment
- 400 participants (estimated)
Sponsor and investigators
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's
- Sponsor type
- University, hospital or other
- Collaborators
- University of Western Ontario, Canada
- Responsible party
- Principal investigator, Eyad AlThenayan, University of Western Ontario, Canada
- Investigators
- Eyad Althenayan, MD, Principal investigator, Western University, CanadaPhilip Jones, MD, FRCPC, Study director, Western University, CanadaBryan Young, MD, FRCPC, Study chair, Western University, CanadaAhmed F Hegazy, MD, FRCPC, Study director, Western University, CanadaAna Igric, MD, FRCSC, Study director, Western University, CanadaCarolyn Benson, MD, Study director, Western University, Canada
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02033733
- Sponsor's protocol ID
- 5511
- Status last verified
- Jan 2014
- First submitted
- 4 Jan 2014
- Last updated
- 13 Jan 2014
- Results posted
- No
- Data monitoring committee
- No
Publications
Sendelbach S, Hearst MO, Johnson PJ, Unger BT, Mooney MR. Effects of variation in temperature management on cerebral performance category scores in patients who received therapeutic hypothermia post cardiac arrest. Resuscitation. 2012 Jul;83(7):829-34. doi: 10.1016/j.resuscitation.2011.12.026. Epub 2012 Jan 8.
PubMed 22230942Werlhof V, Sessler DI. Pancuronium does not decrease oxygen consumption during hypothermic or normothermic cardiopulmonary bypass. Anesth Analg. 1995 Sep;81(3):465-8. doi: 10.1097/00000539-199509000-00006.
PubMed 7653805Peberdy MA, Callaway CW, Neumar RW, Geocadin RG, Zimmerman JL, Donnino M, Gabrielli A, Silvers SM, Zaritsky AL, Merchant R, Vanden Hoek TL, Kronick SL; American Heart Association. Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010 Nov 2;122(18 Suppl 3):S768-86. doi: 10.1161/CIRCULATIONAHA.110.971002.
PubMed 20956225
Study at a glance
From the registry record, last updated by the sponsor on 13 Jan 2014. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Post-arrest Therapeutic Hypothermia. Does Use of Neuromuscular Blockers Achieve Faster Cooling Time?
- ClinicalTrials.gov ID
- NCT02033733
- Acronym / sponsor ID
- 5511
- Keywords
- Post cardiac arrest, Postcardiac arrest therapeutic hypothermia, Therapeutic hypothermia protocol, Neuromuscular blocking agents, Muscle relaxants, Hypothermia-induced increased muscle tone, Microshivering
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 400 participants (estimated)
- Lead sponsor
- London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph'sUniversity, hospital or other
- Collaborators
- University of Western Ontario, Canada
- Study start
- Jan 2014
- Primary completion
- Dec 2014 (estimated)
- Study completion
- Feb 2015 (estimated)
- First posted
- 13 Jan 2014 (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.
After successful resuscitation from cardiac arrest, cooling the whole body is a well established treatment that improves the chances of the brain recovering. This however, has to be done within a certain time-frame from the arrest. The purpose of this study is to explore the best way of dosing the muscle relaxing medications that are given during the cooling process.
Hypothesis: In the context of our institutional therapeutic hypothermia protocol, cisatracurium infusions lead to faster drops in core temperature when compared to cisatracurium prn boluses alone.
Detailed description
STUDY RATIONALE:
A large proportion of comatose survivors of cardiac arrest presenting to our intensive care units at London Health Sciences Centre (LHSC) undergo therapeutic hypothermia. Current evidence suggests that timely achievement of target temperatures is desirable to improve outcomes. At LHSC, this intervention is protocolized with a defined set of preprinted orders that includes a dosing regimen for neuromuscular blocking agents (NMBA's). Our preprinted protocol has been in place since January of 2004. Cisatracurium infusions were part of the therapeutic hypothermia protocol until October 2011. Since that time, our protocol has changed to cisatracurium prn boluses for any observed shivering. In this study we will examine if there has been any change in the times to achieving target temperatures with the implementation of this change. It is important to note that no other change in our protocol has taken place since it was first implemented, making our before and after comparison valid and fair.
Our hypothesis is that NMBA infusions lead to a faster drop in core temperatures when compared to NMBA prn boluses. If this were to stand true, we would expect cisatracurium IV infusions to result in faster reductions in core temperature when compared with cisatracurium prn boluses in the context of our therapeutic hypothermia protocol. Hypothermia has been known to cause a subclinical increase in muscle tone. This previously reported phenomenon has been named "microshivering". When attempting to reduce core temperatures, microshivering is likely a natural body response to try to restore body temperature back to normal. We therefore hypothesize that NMBA infusions are likely more effective at abolishing microshivering, which would be a desirable effect when trying to induce therapeutic hypothermia.
Although current American Heart Association (AHA) guidelines suggest considering the administration of NMBA's to facilitate induced hypothermia and control shivering. Their recommendation is to minimize the duration of NMBA use or if possible, avoid them altogether. After the publication of these guidelines our institutional protocol changed to prn boluses instead of the previous infusion orders. We therefore believe it is important to examine the effects of this change on our cooling protocol and potentially add to the growing body of knowledge in this field.
Study design
- Observational model
- Cohort
- Time perspective
- Retrospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adequate cooling time | – | Drug: Cisatracurium infusion, Drug: Cisatracurium prn bolusPatients that reached target temperature within 4 hours of initiation of the hypothermia protocol will be in the "adequate cooling time" group. |
| Inadequate cooling time | – | Drug: Cisatracurium infusion, Drug: Cisatracurium prn bolusPatients that did not reach target temperature within 4 hours of initiation of the hypothermia protocol will be in the "inadequate cooling time" group. |
Who may qualify
- Ages
- 18 to 90 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
- Study population
- All patients admitted to the intensive care unit (ICU) with a diagnosis of postcardiac arrest between Jan 2008 and Dec 2012 will be examined.
Key inclusion criteria (4 listed)
- Admission to adult ICU (age ≥18 years) at London Health Sciences Centre
- Primary reason for ICU admission: postcardiac arrest
- Both in-hospital and out-of-hospital cardiac arrest will be included
- ICU admission between Jan 2008 and Dec 2012.
Key exclusion criteria (1 listed)
- ICU admissions primarily for reasons other than cardiac arrest.
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 |
|---|---|---|
| Cisatracurium infusionAlso: Neuromuscular blocking agent infusion, NMBA infusion, Continuous NMBA infusion, Continuous cisatracurium infusionThis group will include postcardiac arrest patients that have received a cisatracurium infusion as part of their therapeutic hypothermia protocol. It will only include patients that had their infusion started within 2 hours from protocol initiation. Patients that received an infusion as a rescue measure (beyond the first 2 hours) or did not receive and infusion at all will not be included in this group. Most patients admitted to our ICU postcardiac arrest prior to October 2011, will likely belong to this group (the cisatracurium infusion group). | Drug | Adequate cooling time, Inadequate cooling time |
| Cisatracurium prn bolusAlso: neuromuscular blocking agent prn bolus, NMBA prn bolus, cisatracurium intermittent bolus, intermittent bolus administration of cisatracuriumPatients that have not received a cisatracurium infusion within the first 2 hours from protocol initiation will be in this group. These are likely to be patients admitted to our ICU after October 2011 (when the protocol change happened). | Drug | Adequate cooling time, Inadequate cooling time |
Primary outcome
Time to attaining target temperature (hours).
Time frame: From initiation of hypothermia protocol to reaching a core body temperature of ≤34ºC, assessed up to 72 hours from protocol initiation.
The primary outcome will be a binary outcome that is: adequate cooling time versus inadequate cooling time based on the time needed to achieve target temperatures. We will define adequate cooling time as being ≤ 4 hours from initiation of protocol to reaching target temperature. Inadequate cooling time will be requiring > 4 hours to achieve that goal. Target core body temperature range in our institutional protocol is 32 - 34ºC. The primary outcome will be assessed using a logistic regression model, constructed using covariates affecting speed of cooling as determined by expert opinion and current evidence apriori. The variables will be age, sex, weight, pre-protocol core body temperature, initial arrest rhythm and infusion versus boluses. The model will be used to determine whether the cisatracurium dosing regimen is an independent predictor of adequate patient cooling time or not.
3 secondary outcomes
Cerebral performance category score on hospital discharge.
Time frame: Upon discharge from hospital, assessed up to 36 months postcardiac arrest.
Hospital length of stay postcardiac arrest (days).
Time frame: Days spent in hospital after successful resuscitation from cardiac arrest, assessed up to 36 months from the date of cardiac arrest
Intensive care unit length of stay postcardiac arrest (days).
Time frame: Days spent in the intensive care unit after successful resuscitation from cardiac arrest, assessed up to 36 months from the date of cardiac arrest.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 13 Jan 2014.
- Background: PubMed 22230942Sendelbach S, Hearst MO, Johnson PJ, Unger BT, Mooney MR. Effects of variation in temperature management on cerebral performance category scores in patients who received therapeutic hypothermia post cardiac arrest. Resuscitation. 2012 Jul;83(7):829-34. doi: 10.1016/j.resuscitation.2011.12.026. Epub 2012 Jan 8.
- Background: PubMed 7653805Werlhof V, Sessler DI. Pancuronium does not decrease oxygen consumption during hypothermic or normothermic cardiopulmonary bypass. Anesth Analg. 1995 Sep;81(3):465-8. doi: 10.1097/00000539-199509000-00006.
- Background: PubMed 20956225Peberdy MA, Callaway CW, Neumar RW, Geocadin RG, Zimmerman JL, Donnino M, Gabrielli A, Silvers SM, Zaritsky AL, Merchant R, Vanden Hoek TL, Kronick SL; American Heart Association. Part 9: post-cardiac arrest care: 2010 American Heart Association Guidelines for Cardiopulmonary Resuscitation and Emergency Cardiovascular Care. Circulation. 2010 Nov 2;122(18 Suppl 3):S768-86. doi: 10.1161/CIRCULATIONAHA.110.971002.
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.
Eyad AlThenayan, MD contact
Eyad Althenayan, MD principal investigator
Western University, Canada
Philip Jones, MD, FRCPC study director
Western University, Canada
Bryan Young, MD, FRCPC study chair
Western University, Canada
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Postcardiac Arrest Therapeutic Hypothermia, run by London Health Sciences Centre Research Institute OR Lawson Research Institute of St. Joseph's at 2 sites 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 4 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: status not confirmed, as of the sponsor's last update on 13 Jan 2014. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites 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.
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 Ahmed F Hegazy, MD, FRCPC (1(519) 860-4917, ahmed.hegazy@londonhospitals.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Time to attaining target temperature (hours). (time frame: From initiation of hypothermia protocol to reaching a core body temperature of ≤34ºC, assessed up to 72 hours from protocol initiation.). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT02033733, which also lists 3 linked publications.
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 13 Jan 2014.