PIVOT: Comparing Vasopressin and Adrenaline in Patients With Cardiac Arrest

• Sponsor: Singapore General Hospital (Other)
• Overall Status: Completed
• CT.gov ID: NCT00358579
• Collaborator: National Medical Research Council (NMRC), Singapore (Other), Alexandra Hospital (Other), National University Hospital, Singapore (Other), Changi General Hospital (Other)
• Enrollment: 727
• Locations: 4
• Arms: 2
• Duration (Months): 46.1
• Patients Per Site: 181.8
• Patients Per Site Per Month: 3.9

Study Details

Study Description

Brief Summary

The effectiveness of medications in cardiac arrest has been greatly debated and questioned. Historically intravenous adrenaline has been the drug of choice since 1906. There have been few formal evaluations to determine the value of adrenaline for cardiac arrest, and clinical trials have not been able to show any benefit with intravenous adrenaline (compared to placebo or no treatment) in the field.

Thus the purpose of this study is to compare vasopressin and adrenaline in the treatment of cardiac arrest to answer the question whether there is an improvement in survival between vasopressin and adrenaline.

Condition or Disease	Intervention/Treatment	Phase
Cardiac Arrest	Drug: Adrenaline; Drug: Vasopressin	Phase 3

Detailed Description

The effectiveness of medications in cardiac arrest has been greatly debated and questioned. Historically intravenous adrenaline has been the recommended drug of choice since 1906. There have been few formal evaluations to determine the value of adrenaline for cardiac arrest, and clinical trials have not been able to show any benefit with intravenous adrenaline (compared to placebo or no treatment) in the field.

More recently, vasopressin has been used in patients with cardiac arrest. In human studies on vasopressin, clinical trials have produced conflicting results.

The current study compared vasopressin and adrenaline in the treatment of cardiac arrest in patients presenting to the Emergency Department (ED). Specific outcomes included return of spontaneous circulation (ROSC) (as measured by the presence of a palpable pulse at any time during resuscitation), survival to hospital admission, survival to discharge from hospital, and functional status at discharge and at one year (as measured by the Glasgow-Pittsburgh outcome categories).

Study Design

• Study Type: Interventional
• Actual Enrollment: 727 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Double (Participant, Investigator)
• Primary Purpose: Treatment
• Official Title: A Randomised, Double-blinded Multi-centre Trial Comparing Vasopressin and Adrenaline in Patients With Cardiac Arrest at the Emergency Department. (Preadmission Intravenous Vasopressin, Adrenaline Outcome Trial: PIVOT vII)
• Study Start Date: Mar 1, 2006
• Actual Primary Completion Date: Jan 1, 2009
• Actual Study Completion Date: Jan 1, 2010

Arms and Interventions

Arm	Intervention/Treatment
Active Comparator: Adrenaline	Drug: Adrenaline; 1 mg; Other Names: Epinephrine
Active Comparator: Vasopressin	Drug: Vasopressin; 40 IU; Other Names: Arginine vasopressin argipressin antidiuretic hormone

Outcome Measures

Primary Outcome Measures

1. Survival to Hospital Discharge. [at 30 days post arrest]

   Survival to hospital discharge is defined as the patient leaving the hospital alive or survival to 30 days post cardiac arrest,whichever came first. This therefore measures the number of participants who was discharged alive or survived to 30 days post cardiac arrest, whichever came first.

Secondary Outcome Measures

1. Neurological Status on Discharge or at 30 Days Post Arrest, if Not Discharged. [at 30 days post arrest]

   Neurological status is assessed by the Glasgow-Pittsburgh outcome categories, to evaluate quality of life after successful resuscitation. Good neurological status is defined as cerebral performance categories(CPC)/overall performance categories(OPC):1 and 2.CPC/OPC 1 indicates good cerebral & overall performance. CPC/OPC 2 indicates moderate cerebral & overall disability. CPC/OPC 3 indicates severe cerebral & overall disability. CPC/OPC 4 indicates coma, vegetative state. CPC/OPC 5 indicates brain dead/death.

2. Neurological Status at 1 Year. [at 1 year post arrest]

   Neurological status is assessed by the Glasgow-Pittsburgh outcome categories, to evaluate quality of life after successful resuscitation. Good neurological status is defined as cerebral performance categories(CPC)/overall performance categories(OPC): 1 and 2. CPC/OPC 1 indicates good cerebral & overall performance. CPC/OPC 2 indicates moderate cerebral & overall disability. CPC/OPC 3 indicates severe cerebral & overall disability. CPC/OPC 4 indicates coma, vegetative state. CPC/OPC 5 indicates brain dead/death.

3. Return of Spontaneous Circulation. [during resuscitation]

   Return of spontaneous circulation is defined as the presence of any palpable pulse detected by manual palpation of a major artery. This is measured as number of participants who had return of spontaneous circulation during resuscitation.

4. Survival to Admission. [No specific time frame. Survival to admission refers to sustained return of spontaneous circulation until admission and transfer of care to Intensive Care Units /wards]

   Survival to admission is defined as the presence of pulse on admission to hospital (discharged from Emergency Department and admitted to Intensive Care Units /wards). This measures the number of participants with pulse and who were admitted to hospital.

Eligibility Criteria

Criteria

• Ages Eligible for Study: 17 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

• Patient with cardiac arrest as confirmed by the absence of a pulse, unresponsiveness and apnea

• Age above 16 (Age 21 and above for CGH only)

Exclusion Criteria:

• Traumatic cardiac arrest

• Age 16 and below (Age 20 and below for CGH only)

• CPR is contraindicated

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	National University Hospital	Singapore		Singapore	119074
2	Alexandra Hospital	Singapore		Singapore	159964
3	Singapore General Hospital	Singapore		Singapore	169608
4	Changi General Hospital	Singapore		Singapore	529889

Sponsors and Collaborators

• Singapore General Hospital
• National Medical Research Council (NMRC), Singapore
• Alexandra Hospital
• National University Hospital, Singapore
• Changi General Hospital

Investigators

• Principal Investigator: Marcus EH Ong, MBBS, Singapore General Hospital

Study Documents (Full-Text)

None provided.

More Information

Publications

None provided.

• Responsible Party: Singapore General Hospital
• ClinicalTrials.gov Identifier: NCT00358579
• Other Study ID Numbers: SQCA01
• First Posted: Aug 1, 2006
• Last Update Posted: Mar 17, 2017
• Last Verified: Feb 1, 2017

• Keywords provided by Singapore General Hospital: Vasopressin; Adrenaline; Survival; Return of spontaneous of circulation
• Additional relevant MeSH terms: Heart Arrest; Vasopressins; Arginine Vasopressin; Epinephrine; Racepinephrine; Epinephryl borate

Study Results

Participant Flow

Recruitment Details	The recruitment period was from 9 March 2006 to 19 January 2009. Location of recruitment was in emergency departments.
Pre-assignment Detail	The exclusion criteria included traumatic cardiac arrest or when cardiopulmonary resuscitation was contraindicated; for example those 'obviously dead' as defined by the presence of decomposition, rigor mortis or dependant lividity. Participants below the age of 16 years old were not included in the study

Arm/Group Title	Adrenaline	Vasopressin
Arm/Group Description	1 mg Intravenous Adrenaline, administered as the first drug upon cardiac arrest patient's arrival at the Emergency Department	40 IU Intravenous Vasopressin, administered as the first drug upon cardiac arrest patient's arrival at the Emergency Department
Period Title: Overall Study
STARTED	353	374
COMPLETED	353	374
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Adrenaline	Vasopressin	Total
Arm/Group Description	1 mg Intravenous Adrenaline, administered as the first drug upon cardiac arrest patient's arrival at the Emergency Department	40 IU Intravenous Vasopressin, administered as the first drug upon cardiac arrest patient's arrival at the Emergency Department	Total of all reporting groups
Overall Participants	353	374	727
Age (Count of Participants)
<=18 years	1 0.3%	0 0%	1 0.1%
Between 18 and 65 years	170 48.2%	186 49.7%	356 49%
>=65 years	182 51.6%	188 50.3%	370 50.9%
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	64.9 (15.4)	64.6 (14.2)	64.7 (14.8)
Sex: Female, Male (Count of Participants)
Female	111 31.4%	111 29.7%	222 30.5%
Male	242 68.6%	263 70.3%	505 69.5%
Region of Enrollment (participants) [Number]
Singapore	353 100%	374 100%	727 100%

Outcome Measures

1. Primary Outcome

Title	Survival to Hospital Discharge.
Description	Survival to hospital discharge is defined as the patient leaving the hospital alive or survival to 30 days post cardiac arrest,whichever came first. This therefore measures the number of participants who was discharged alive or survived to 30 days post cardiac arrest, whichever came first.
Time Frame	at 30 days post arrest

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adrenaline	Vasopressin
Arm/Group Description	1 mg Intravenous Adrenaline, administered as the first drug upon cardiac arrest patient's arrival at the Emergency Department	40 IU Intravenous Vasopressin, administered as the first drug upon cardiac arrest patient's arrival at the Emergency Department
Measure Participants	353	374
Number [Participants]	8 2.3%	11 2.9%

2. Secondary Outcome

Title	Neurological Status on Discharge or at 30 Days Post Arrest, if Not Discharged.
Description	Neurological status is assessed by the Glasgow-Pittsburgh outcome categories, to evaluate quality of life after successful resuscitation. Good neurological status is defined as cerebral performance categories(CPC)/overall performance categories(OPC):1 and 2.CPC/OPC 1 indicates good cerebral & overall performance. CPC/OPC 2 indicates moderate cerebral & overall disability. CPC/OPC 3 indicates severe cerebral & overall disability. CPC/OPC 4 indicates coma, vegetative state. CPC/OPC 5 indicates brain dead/death.
Time Frame	at 30 days post arrest

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adrenaline	Vasopressin
Arm/Group Description	1 mg Intravenous Adrenaline, administered as the first drug upon cardiac arrest patient's arrival at the Emergency Department	40 IU Intravenous Vasopressin, administered as the first drug upon cardiac arrest patient's arrival at the Emergency Department
Measure Participants	353	374
Cerebral Performance Categories 1	5 1.4%	4 1.1%
Cerebral Performance Categories 2	0 0%	1 0.3%
Overall Performance Categories 1	2 0.6%	5 1.3%
Overall Performance Categories 2	3 0.8%	0 0%

3. Secondary Outcome

Title	Neurological Status at 1 Year.
Description	Neurological status is assessed by the Glasgow-Pittsburgh outcome categories, to evaluate quality of life after successful resuscitation. Good neurological status is defined as cerebral performance categories(CPC)/overall performance categories(OPC): 1 and 2. CPC/OPC 1 indicates good cerebral & overall performance. CPC/OPC 2 indicates moderate cerebral & overall disability. CPC/OPC 3 indicates severe cerebral & overall disability. CPC/OPC 4 indicates coma, vegetative state. CPC/OPC 5 indicates brain dead/death.
Time Frame	at 1 year post arrest

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adrenaline	Vasopressin
Arm/Group Description	1 mg Intravenous Adrenaline, administered as the first drug upon cardiac arrest patient's arrival at the Emergency Department	40 IU Intravenous Vasopressin, administered as the first drug upon cardiac arrest patient's arrival at the Emergency Department
Measure Participants	353	374
Cerebral Performance Categories 1	5 1.4%	4 1.1%
Cerebral Performance Categories 2	0 0%	1 0.3%
Overall Performance Categories 1	3 0.8%	3 0.8%
Overall Performance Categories 2	2 0.6%	1 0.3%

4. Secondary Outcome

Title	Return of Spontaneous Circulation.
Description	Return of spontaneous circulation is defined as the presence of any palpable pulse detected by manual palpation of a major artery. This is measured as number of participants who had return of spontaneous circulation during resuscitation.
Time Frame	during resuscitation

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adrenaline	Vasopressin
Arm/Group Description	1 mg Intravenous Adrenaline, administered as the first drug upon cardiac arrest patient's arrival at the Emergency Department	40 IU Intravenous Vasopressin, administered as the first drug upon cardiac arrest patient's arrival at the Emergency Department
Measure Participants	353	374
Number [Participants]	106 30%	119 31.8%

5. Secondary Outcome

Title	Survival to Admission.
Description	Survival to admission is defined as the presence of pulse on admission to hospital (discharged from Emergency Department and admitted to Intensive Care Units /wards). This measures the number of participants with pulse and who were admitted to hospital.
Time Frame	No specific time frame. Survival to admission refers to sustained return of spontaneous circulation until admission and transfer of care to Intensive Care Units /wards

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Adrenaline	Vasopressin
Arm/Group Description	1 mg Intravenous Adrenaline, administered as the first drug upon cardiac arrest patient's arrival at the Emergency Department	40 IU Intravenous Vasopressin, administered as the first drug upon cardiac arrest patient's arrival at the Emergency Department
Measure Participants	353	374
Number [Participants]	59 16.7%	83 22.2%

Adverse Events

Adverse Event Reporting Description	Serious and other adverse events were not collected or assessed as it is not applicable to this study, which recruits patients in cardiac arrest (low survival rate).
Arm/Group Title	Adrenaline		Vasopressin
Arm/Group Description	1 mg Intravenous Adrenaline, administered as the first drug upon cardiac arrest patient's arrival at the Emergency Department		40 IU Intravenous Vasopressin, administered as the first drug upon cardiac arrest patient's arrival at the Emergency Department
All Cause Mortality
	Adrenaline		Vasopressin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	/ (NaN)		/ (NaN)
Serious Adverse Events
	Adrenaline		Vasopressin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)
Other (Not Including Serious) Adverse Events
	Adrenaline		Vasopressin
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/0 (NaN)		0/0 (NaN)

Limitations/Caveats

As the study was conducted over a relatively long period, results may be affected by secular trends.Variations in post-resuscitation care can affect survival to discharge status and variations between institutions are difficult to account for.

More Information

Certain Agreements

Principal Investigators are NOT employed by the organization sponsoring the study.

There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.