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Morphine or/and Ketamine in Out-of-hospital Cardiac Arrest

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT04009759
Recruitment Status : Not yet recruiting
First Posted : July 5, 2019
Last Update Posted : July 5, 2019
Sponsor:
Information provided by (Responsible Party):
Vladimir Kuklin, University Hospital, Akershus

Brief Summary:
Preclinical studies demonstrate that opioids can preserve cellular integrity status during acute hypoxia in many organs and tissues including: intestine, skeletal muscle, myocardium and brain. Morphine has been shown to significantly increase the survival of mice and rats in acute hypoxia conditions. In the experimental model with rats exposed to hypoxic gas (5% oxygen, 95% N2) for 70 min, all seven rats in the naloxone pre-treated group died at the end of the experiments while only one out of seven rats died in the Morphine (5 mg/kg) pretreated group, and five from the seven rats died in the control group. In the experiments where the rats were exposed to 8 min anoxia, pre-treatment with Morphine (5mg/kg), or Ketamine (40 mg/kg), resulted in higher survival in both groups as compared to the control group (data not yet published). No publications looking at the survival rate in animals with treatment by Morphine before cardiac arrest have been published yet. Meanwhile, two recent retrospective studies demonstrated that patients who were treated with opioids before or during cardiac arrest had a statistically significantly higher survival rate and much better neurological outcome compared to untreated patients. As it is not possible to apply cardiac arrest to animal without any anaesthesia (main limitation of all experimental models of cardiac arrest), the sympathomimetic effects and possible neuroprotective features of Ketamine should be tested in patients with cardiac arrest. Additional topic for possible clinical research of Ketamine as well as Morphine could be their analgesic effects as vigorous thoracic compression with possible trauma of the ribs may lead to severe pain and stress related negative body responses in patients surviving CPR.

Condition or disease Intervention/treatment Phase
Cardiac Arrest Drug: Morphine Drug: Ketamine Injectable Solution Drug: Saline 0.9% Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 2100 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Intervention Model Description: Adult patients who have sustained an out-of-hospital cardiac arrest for which advanced life support will be provided by skilled paramedics or prehospital trained anaesthesiologists will be eligible for inclusion.
Masking: Single (Outcomes Assessor)
Masking Description: Every ambulance car or helicopter on duty in the city of Oslo and Vestre Viken Hospital Trust will have a trial pack containing 10 pre-filled 10 ml syringes that will be labeled with only randomisation number. Paramedics or prehospital trained anaesthesiologists will not know the content of the syringes as well as a meaning of the randomisation number. The pharmacy of Akershus university hospital will be responsible to prepare the syringes.
Primary Purpose: Treatment
Official Title: Treatment of Patients With Morphine or/and Ketamine During Out-of-hospital Cardiac Pulmonary Resuscitation
Estimated Study Start Date : January 1, 2020
Estimated Primary Completion Date : January 1, 2025
Estimated Study Completion Date : January 1, 2026

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Active Comparator: Morphine
Morphine group (n=700), where patients will be treated with i.v. injection of Morphine 2,5 mg diluted in 10 ml of NaCl 0,9%. The treatment will be given during CPR as soon as possible.
Drug: Morphine
Adult patients with an out-of-hospital cardiac arrest will be evaluated by skilled paramedics or prehospital trained anaesthesiologists for inclusions criteria to the study and randomised to get the blinded study medicine as addition to standard treatment of cardiac arrest. Randomization will be performed by means of sealed envelopes containing number of syringe that will be used.

Active Comparator: Ketamine
Ketamine group (n=700), where patients will be treated with i.v. injection of Ketamine 50 mg diluted in 10 ml of NaCl 0,9%. The treatment will be given during CPR as soon as possible.
Drug: Ketamine Injectable Solution
Adult patients with an out-of-hospital cardiac arrest will be evaluated by skilled paramedics or prehospital trained anaesthesiologists for inclusions criteria to the study and randomised to get the blinded study medicine as addition to standard treatment of cardiac arrest. Randomization will be performed by means of sealed envelopes containing number of syringe that will be used.
Other Name: Ketamine

Placebo Comparator: Saline
Control group (n=700), where patients will be treated with i.v. 10 ml of NaCl 0,9%. The treatment will be given during CPR as soon as possible.
Drug: Saline 0.9%
Adult patients with an out-of-hospital cardiac arrest will be evaluated by skilled paramedics or prehospital trained anaesthesiologists for inclusions criteria to the study and randomised to get the blinded study medicine as addition to standard treatment of cardiac arrest. Randomization will be performed by means of sealed envelopes containing number of syringe that will be used.
Other Name: Saline




Primary Outcome Measures :
  1. Survival at 30 days in patients after out-ofhospital cardiac arrest [ Time Frame: 30 days ]
    Survival rate at 30 days in patients after out-ofhospital cardiac arrest treated or not with Morphine or ketamine during CPR


Secondary Outcome Measures :
  1. Measurement of biochemical markers of brain damage (NSE, S-100B protein) [ Time Frame: 2,12, 24 and 48 hours ]
    Measurement of biochemical markers of brain damage (NSE, S-100B protein) at 2,12, 24 and 48 hours in patients after out-of-hospital cardiac arrest.

  2. Length of stay in the intensive care unit [ Time Frame: 3 month ]
    Registration of length of patients stay (days) in the intensive care units

  3. Length of stay in the hospital [ Time Frame: 3 months ]
    Registration of patients stay (days) in the hospitals

  4. Survival rate at 3 months after cardiac arrest [ Time Frame: 3 months ]
    Registration of survival rate at 3 months after cardiac arrest

  5. Neurological outcome at the hospital discharge [ Time Frame: 6 months ]

    Modified Rankin Scale (mRS) will be used for evaluation of neurological outcome. The mRS-9Q Survey and web calculator / error-checker can be accessed freely at:

    www.modifiedrankin.com. The mRS score encodes meaningful levels of function from no symptoms or functional impairment (mRS score = 0) through to severe disability requiring constant nursing care (mRS score = 5). the mRS-9Q is an easy-to-use tool to determine the mRS score with very good interobserver reliability and reproducibility. Web-based calculator can be also administered by personnel without clinical training, either in person or by telephone.


  6. neurological outcome at 3 months after cardiac arrest [ Time Frame: 3 months ]

    Modified Rankin Scale (mRS) will be used for evaluation of neurological outcome. The mRS-9Q Survey and web calculator / error-checker can be accessed freely at:

    www.modifiedrankin.com. The mRS score encodes meaningful levels of function from no symptoms or functional impairment (mRS score = 0) through to severe disability requiring constant nursing care (mRS score = 5). the mRS-9Q is an easy-to-use tool to determine the mRS score with very good interobserver reliability and reproducibility. Web-based calculator can be also administered by personnel without clinical training, either in person or by telephone.




Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

- All adult patients with out-of-hospital cardiac arrest

Exclusion Criteria:

  • an age of less than 18 years
  • cardiac arrest from myocardial infarction (if it can be expected to give Morphine during CPR as a part of the MONA therapy)
  • drugs poisoning or the administration of opioids or Ketamine 24 hours before the cardiac arrest
  • terminal phase of oncological or other chronic diseases
  • poor communication and physical capabilities due to psychiatric or neurological diseases
  • dementia or Alzheimers
  • extremely reduced weight or physical ability and activity
  • known history of chronic use of opioids/Ketamine

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT04009759


Contacts
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Contact: Vladimir Kuklin, dr med +4798838024 vkuklin@me.com
Contact: Lisa Dybvik, cand med +4746669271 ldybvik@hotmail.com

Sponsors and Collaborators
University Hospital, Akershus

Additional Information:
Publications:

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Responsible Party: Vladimir Kuklin, Head of day case surgery unit, University Hospital, Akershus
ClinicalTrials.gov Identifier: NCT04009759    
Other Study ID Numbers: Akershus university hospital
First Posted: July 5, 2019    Key Record Dates
Last Update Posted: July 5, 2019
Last Verified: July 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No
Keywords provided by Vladimir Kuklin, University Hospital, Akershus:
cardiac arrest
Morphine
Ketamine
Survival rate
Additional relevant MeSH terms:
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Heart Arrest
Heart Diseases
Cardiovascular Diseases
Ketamine
Morphine
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anesthetics, Dissociative
Anesthetics, Intravenous
Anesthetics, General
Anesthetics
Central Nervous System Depressants
Excitatory Amino Acid Antagonists
Excitatory Amino Acid Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Analgesics, Opioid
Narcotics