Therapeutic Hypothermia With Propofol in Survival and Neurological Prognoses After Cardiac Arrest

Cardiac Arrest Clinical Trial

Official title:

Combining Propofol With Therapeutic Hypothermia for Improving Survival and Neurological Prognoses in Patients Resuscitated From Cardiac Arrest

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT02367755
• Other study ID #: 102060-F_102-FTN12
• Status: Recruiting
• Phase: Phase 4
• First received: February 2, 2015
• Last updated: March 26, 2016
• Start date: August 2013
• Est. completion date: December 2016

Study information

• Verified date: March 2016
• Source: Far Eastern Memorial Hospital
• Contact: Yen-Wen Wu, MD, PhD
• Phone: 886-2-8966-7000
• Email: wuyw0502[@]gmail.com
• Is FDA regulated: No
• Health authority: Taiwan: Institutional Review Board
• Study type: Interventional

Clinical Trial Summary

Therapeutic hypothermia has been proven to significantly improve the survival and neurological prognoses in patients resuscitated from cardiac arrest. Propofol has been reported to exhibit potentials in mitigating ischemia-reperfusion injury via the antioxidative, anti-inflammatory and neuroprotective mechanisms. This study is to investigate the potentials of propofol in further improving the survival and neurological prognoses in this era of therapeutic hypothermia.

Description:

Cardiac arrest and cardiopulmonary resuscitation (CPR) is a specific model of global ischemia/reperfusion (I/R) injury. Among all organ systems, brain is least tolerable to ischemic insult and I/R injury, which accounts for the usually poor survival and neurological outcomes in these patients even with initial success in resuscitation. Therapeutic hypothermia (TH) has been proven to significantly improve the survival and neurological prognoses in patients resuscitated from cardiac arrest. It has been recommended as a standard therapy in the post-resuscitation care since 2002. In the past few years, NTUH and FEMH have been actively promoted the application of TH in the post-resuscitation care, and both have achieved important progress. Based on these, the investigators seek to further improve the survival and neurological outcomes in this group of patients. Among the therapies with potential additive or synergistic protective mechanisms, propofol has been extensively studied, and shown to exhibit great potentials in mitigating ischemia-reperfusion injury via the antioxidative, anti-inflammatory and neuroprotective mechanisms. As sedatives are basic requirement during TH according to technical and ethical concerns, the combination of propofol and TH is not only justified but highly anticipated. The investigators therefore seek to investigate the potentials of propofol in further improving the survival and neurological prognoses in this era of therapeutic hypothermia.

Methods: This .is a prospective, single-blinded randomized clinical trial. The inclusion criteria include: (1) non-traumatic cardiac arrest (2) no regain of consciousness after return of spontaneous circulation (ROSC) (3) age >=20 years old and <= 90 years old. The exclusion criteria include (1) age < 20 y/o or > 90 y/o (2) pregnancy (3) traumatic cardiac arrest (4) fail to achieve ROSC (5) conscious recovery after ROSC (6) contraindications for TH, such as massive bleeding, infections, etc (7) terminal diseases (8) conscious disturbance before cardiac arrest (9) fail to obtain informed consent (10) families refuse to undergo clinical trial. The study will be divided to two groups: (1) Lorazepam group: lorazepam infusion at a rate of 0.5 mg/kg/hr during TH. (2) Propofol group: propofol infusion at a rate of 3 mg/kg/hr during TH. The primary endpoints will be (1) survival (2) neurological outcomes as indicated by cerebral performance category (CPC) scale. The secondary endpoints include (1) 99mTc ECD scan (perfusion and viability), (2) clinical and EEG evidences of seizure. The blood pressure and heart rate will continuously monitored during TH and propofol/lorazepam infusion.

Expected Results: (1) Test if propofol further improves the survival and neurological outcomes in post-CPR patients undergoing TH (2) Test if propofol further improves cerebral perfusion and neuron viability in post-CPR patients undergoing TH (3) Test if propofol reduces the incidence and severity of seizures post-CPR, (4) Test if propofol significantly influence hemodynamics when combined with TH Clinical Implications: Propofol is a clinically available sedative agent. If this trial demonstrates that propofol further improves the survival and neurological outcomes in post-resuscitation patients undergoing TH, it would become an important evidence justifying implementation in clinical practice

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: December 2016
• Est. primary completion date: December 2016
• Accepts healthy volunteers: No
• Gender: Both
• Age group: 20 Years and older

Eligibility

Inclusion criteria:

1. non-traumatic cardiac arrest

2. no regain of consciousness after return of spontaneous circulation (ROSC)

3. age >=20 years old and <= 90 years old.

Exclusion criteria:

1. age < 20 y/o or > 90 y/o

2. pregnancy

3. traumatic cardiac arrest

4. fail to achieve ROSC

5. conscious recovery after ROSC

6. contraindications for TH, such as massive bleeding, infections, etc

7. terminal diseases

8. conscious disturbance before cardiac arrest

9. fail to obtain informed consent

10. families refuse to undergo clinical trial

11. allergy to propofol or lorazepam.

Study Design

Allocation: Randomized, Endpoint Classification: Safety/Efficacy Study, Intervention Model: Parallel Assignment, Masking: Open Label, Primary Purpose: Treatment

Related Conditions & MeSH terms

• Cardiac Arrest
• Heart Arrest
• Hypothermia

Intervention

Drug:
• Propofol
Propofol use during therapeutic hypothermia
• Lorazepam
Lorazepam use during therapeutic hypothermia

Locations

Country	Name	City	State
Taiwan	Far Eastern Memorial Hospital	New Taipei City

Sponsors (1)

Lead Sponsor	Collaborator
Far Eastern Memorial Hospital

Country where clinical trial is conducted

Taiwan, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Neurologic statue at discharge	Glasgow score, cerebral performance category scale	at dicharge	No
Secondary	Brain SPECT The standard 99mTc-ethylene L-cysteinate dimer [ECD] will be done on day 5-14 post-resuscitation. The perfusion will be assessed, and the viability of the cerebral tissue will be interpreted using SPECT, by 2 experienced nuclear m	Regional Scores of Tc-99m ECD Brain SPECT	day 5-14 post-resuscitation	No
Secondary	From ROSC to recovery of consciousness	Recovery of consciousness: being able to follow orders. participants will be followed for the duration of hospital stay, an expected average of 4 weeks.	participants will be followed for the duration of hospital stay, an expected average of 4 weeks	No
Secondary	Survival to discharge		participants will be followed for the duration of hospital stay, an expected average of 4 weeks	No