VAM-IHCA: Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest

• Sponsor: Lars Wiuff Andersen (Other)
• Overall Status: Completed
• CT.gov ID: NCT03640949
• Collaborator: University of Aarhus (Other)
• Enrollment: 501
• Locations: 10
• Arms: 2
• Actual Duration (Months): 40.1
• Patients Per Site: 50.1
• Patients Per Site Per Month: 1.2

Study Details

Study Description

Brief Summary

This is an investigator-initiated, multicenter, randomized, placebo-controlled, parallel group, double-blind, superiority trial of vasopressin and methylprednisolone during adult in-hospital cardiac arrest. There will be ten enrolling sites in Denmark. 492 adult patients with in-hospital cardiac arrest receiving at least one dose of adrenaline will be enrolled. The primary outcome is return of spontaneous circulation and key secondary outcomes include survival at 30 days and survival at 30 days with a favorable neurological outcome.

Condition or Disease	Intervention/Treatment	Phase
Heart Arrest	Drug: Vasopressin, Arginine; Drug: Methylprednisolone; Drug: NaCl	Phase 2/Phase 3

Study Design

• Study Type: Interventional
• Actual Enrollment: 501 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
• Primary Purpose: Treatment
• Official Title: Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest - A Randomized, Double-Blind, Placebo-Controlled Trial
• Actual Study Start Date: Sep 17, 2018
• Actual Primary Completion Date: Jan 21, 2021
• Actual Study Completion Date: Jan 21, 2022

Arms and Interventions

Arm	Intervention/Treatment
Experimental: Vasopressin and methylprednisolone The study drugs will consist of 40 mg methylprednisolone (Solu-medrol®, Pfizer) and 20 IU of vasopressin (Empressin®, Amomed Pharma GmbH) given as soon as possible after the first dose of adrenaline. Additional doses of vasopressin (20 IU) will be administered after each adrenaline dose for a maximum of four doses (80 IU).	Drug: Vasopressin, Arginine; 20 IE of vasopressin per dose for a maximum of four doses (80 IU); Drug: Methylprednisolone; 40 mg methylprednisolone once
Placebo Comparator: Placebo The placebo for vasopressin will consist of 1 mL of 9 mg/mL NaCl ("normal saline") from 2 mL ampules identical to the vasopressin ampules. The placebo for methylprednisolone will also consist of 1 mL of 9 mg/mL NaCl.	Drug: NaCl; Placebo

Outcome Measures

Primary Outcome Measures

1. Number of Participants With Return of Spontaneous Circulation [During the cardiac arrest, an average of 20 minutes]

   Return of spontaneous circulation is defined as spontaneous circulation with no further need for chest compressions sustained for at least 20 minutes

Secondary Outcome Measures

1. Number of Participants That Survived 30 Days [At 30 days]

2. Number of Participants With a Favorable Neurological Outcome at 30 Days [At 30 days]

   A favorable neurological outcome will be defined as a cerebral performance category score of 1 or 2. The cerebral performance category score is a 5-point scale assessing neurological/functional outcomes after brain damage with higher scores indicating worse neurological/functional outcomes.

Other Outcome Measures

1. Vasopressor-free Days [7 days]

   Vasopressor-free days will be defined as the number of days within the first 7 days after the cardiac arrest where the patient is not receiving vasopressors and is alive.

2. Invasive Ventilation-free Days [7 days]

   Invasive ventilation-free days will be defined as the number of days within the first 7 days after the cardiac arrest where the patient is not receiving invasive ventilation and is alive.

3. Sequential Organ Failure Assessment (SOFA) Score at 24, 48 and 72 Hours [24, 48 and 72 hours]

   The SOFA score is a validated and widely used measure of organ failure assessing the respiratory, nervous, cardiovascular, hepatic, coagulation, and renal systems. We will assess both the cardiovascular sub score as well as the overall SOFA score.

4. Hospital Disposition [At hospital discharge, up to 1 year]

   Hospital disposition (e.g. home, rehabilitation, nursing home, hospice) will be defined at the time of discharge from the initial acute care hospital.

5. Survival [At 90 days, 180 days, and 1 year]

6. Favorable Neurological Outcome [At 90 days, 180 days, and 1 year]

   A favorable neurological outcome will be defined as a cerebral performance category score of 1 or 2. The cerebral performance category score is a 5-point scale assessing neurological/functional outcomes after brain damage with higher scores indicating worse neurological/functional outcomes.

7. Modified Rankin Scale (mRS) [At 30 days, 90 days, 180 days, and 1 year]

   The mRS is a 7-point scale, ranging from 0 (no symptoms) to 6 (dead), assessing the degree of disability and dependence after a neurological injury such as stroke or cardiac arrest. A good outcome will be defined as a mRS of 0 to 3 and a poor outcome as 4 to 6.

8. Glasgow Outcome Scale Extended (GOSE) [At 30 days, 90 days, 180 days, and 1 year]

   The GOSE is a 8-point scale that is an extension of the Glasgow Outcomes Scale (which is identical to the CPC, only with inverse scores) where the scores 1, 2 and 3 from the CPC score is divided into two.

9. Health-related Quality of Life (EQ-5D-5L) [At 30 days, 90 days, 180 days, and 1 year]

   The EQ-5D-5L is a well-established measure of health-related quality of life that is quantified as a utility (i.e. a measure of quality of life between 0 and 1).

Eligibility Criteria

Criteria

• Ages Eligible for Study: 18 Years and Older
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Inclusion Criteria:

1. In-hospital cardiac arrest

2. Age ≥ 18 years

3. Received at least one dose of adrenaline during cardiopulmonary resuscitation

Exclusion Criteria:

1. Clearly documented "do-not-resuscitate" order prior to the cardiac arrest

2. Prior enrollment in the trial

3. Invasive mechanical circulatory support at the time of the cardiac arrest

4. Known or suspected pregnancy at the time of the cardiac arrest

Contacts and Locations

Locations

	Site	City	State	Country	Postal Code
1	Aalborg University Hospital	Aalborg		Denmark
2	Aarhus University Hospital	Aarhus		Denmark
3	Copenhagen University Hospital - Rigshospitalet	Copenhagen		Denmark
4	Copenhagen University Hospital - Gentofte	Hellerup		Denmark
5	Copenhagen University Hospital - Herlev	Herlev		Denmark
6	Horsens Regional Hospital	Horsens		Denmark
7	Zealand University Hospital - Køge	Køge		Denmark
8	Odense University Hospital	Odense		Denmark
9	Randers Regional Hospital	Randers		Denmark
10	Viborg Regional Hospital	Viborg		Denmark

Sponsors and Collaborators

• Lars Wiuff Andersen
• University of Aarhus

Investigators

• Principal Investigator: Lars W Andersen, MD, MPH, PhD, DMSc, Aarhus University Hospital

Study Documents (Full-Text)

• Study Protocol and Statistical Analysis Plan - Oct 30, 2020

More Information

Additional Information:

• Trial website

Publications

None provided.

• Responsible Party: Lars Wiuff Andersen, Associate Professor, Aarhus University Hospital
• ClinicalTrials.gov Identifier: NCT03640949
• Other Study ID Numbers: 00001; 2017-004773-13
• First Posted: Aug 21, 2018
• Last Update Posted: Mar 2, 2022
• Last Verified: Feb 1, 2022

• Individual Participant Data (IPD) Sharing Statement: Yes
• Plan to Share IPD: Yes
• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No
• Additional relevant MeSH terms: Heart Arrest; Methylprednisolone; Vasopressins; Arginine Vasopressin

Study Results

Participant Flow

Arm/Group Title	Vasopressin and Methylprednisolone	Placebo
Arm/Group Description	The study drugs will consist of 40 mg methylprednisolone (Solu-medrol®, Pfizer) and 20 IU of vasopressin (Empressin®, Amomed Pharma GmbH) given as soon as possible after the first dose of adrenaline. Additional doses of vasopressin (20 IU) will be administered after each adrenaline dose for a maximum of four doses (80 IU). Vasopressin, Arginine: 20 IE of vasopressin per dose for a maximum of four doses (80 IU) Methylprednisolone: 40 mg methylprednisolone once	The placebo for vasopressin will consist of 1 mL of 9 mg/mL NaCl ("normal saline") from 2 mL ampules identical to the vasopressin ampules. The placebo for methylprednisolone will also consist of 1 mL of 9 mg/mL NaCl. NaCl: Placebo
Period Title: Overall Study
STARTED	237	264
COMPLETED	237	264
NOT COMPLETED	0	0

Baseline Characteristics

Arm/Group Title	Vasopressin and Methylprednisolone	Placebo	Total
Arm/Group Description	The study drugs will consist of 40 mg methylprednisolone (Solu-medrol®, Pfizer) and 20 IU of vasopressin (Empressin®, Amomed Pharma GmbH) given as soon as possible after the first dose of adrenaline. Additional doses of vasopressin (20 IU) will be administered after each adrenaline dose for a maximum of four doses (80 IU). Vasopressin, Arginine: 20 IE of vasopressin per dose for a maximum of four doses (80 IU) Methylprednisolone: 40 mg methylprednisolone once	The placebo for vasopressin will consist of 1 mL of 9 mg/mL NaCl ("normal saline") from 2 mL ampules identical to the vasopressin ampules. The placebo for methylprednisolone will also consist of 1 mL of 9 mg/mL NaCl. NaCl: Placebo	Total of all reporting groups
Overall Participants	237	264	501
Age (years) [Mean (Standard Deviation) ]
Mean (Standard Deviation) [years]	71 (13)	70 (12)	71 (13)
Sex: Female, Male (Count of Participants)
Female	89 37.6%	90 34.1%	179 35.7%
Male	148 62.4%	174 65.9%	322 64.3%
Race and Ethnicity Not Collected (Count of Participants)
Count of Participants [Participants]	0 0%

Outcome Measures

1. Primary Outcome

Title	Number of Participants With Return of Spontaneous Circulation
Description	Return of spontaneous circulation is defined as spontaneous circulation with no further need for chest compressions sustained for at least 20 minutes
Time Frame	During the cardiac arrest, an average of 20 minutes

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vasopressin and Methylprednisolone	Placebo
Arm/Group Description	The study drugs will consist of 40 mg methylprednisolone (Solu-medrol®, Pfizer) and 20 IU of vasopressin (Empressin®, Amomed Pharma GmbH) given as soon as possible after the first dose of adrenaline. Additional doses of vasopressin (20 IU) will be administered after each adrenaline dose for a maximum of four doses (80 IU). Vasopressin, Arginine: 20 IE of vasopressin per dose for a maximum of four doses (80 IU) Methylprednisolone: 40 mg methylprednisolone once	The placebo for vasopressin will consist of 1 mL of 9 mg/mL NaCl ("normal saline") from 2 mL ampules identical to the vasopressin ampules. The placebo for methylprednisolone will also consist of 1 mL of 9 mg/mL NaCl. NaCl: Placebo
Measure Participants	237	264
Number [participants]	100 42.2%	86 32.6%

2. Secondary Outcome

Title	Number of Participants That Survived 30 Days
Time Frame	At 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vasopressin and Methylprednisolone	Placebo
Arm/Group Description	The study drugs will consist of 40 mg methylprednisolone (Solu-medrol®, Pfizer) and 20 IU of vasopressin (Empressin®, Amomed Pharma GmbH) given as soon as possible after the first dose of adrenaline. Additional doses of vasopressin (20 IU) will be administered after each adrenaline dose for a maximum of four doses (80 IU). Vasopressin, Arginine: 20 IE of vasopressin per dose for a maximum of four doses (80 IU) Methylprednisolone: 40 mg methylprednisolone once	The placebo for vasopressin will consist of 1 mL of 9 mg/mL NaCl ("normal saline") from 2 mL ampules identical to the vasopressin ampules. The placebo for methylprednisolone will also consist of 1 mL of 9 mg/mL NaCl. NaCl: Placebo
Measure Participants	237	264
Count of Participants [Participants]	23 9.7%	31 11.7%

3. Secondary Outcome

Title	Number of Participants With a Favorable Neurological Outcome at 30 Days
Description	A favorable neurological outcome will be defined as a cerebral performance category score of 1 or 2. The cerebral performance category score is a 5-point scale assessing neurological/functional outcomes after brain damage with higher scores indicating worse neurological/functional outcomes.
Time Frame	At 30 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title	Vasopressin and Methylprednisolone	Placebo
Arm/Group Description	The study drugs will consist of 40 mg methylprednisolone (Solu-medrol®, Pfizer) and 20 IU of vasopressin (Empressin®, Amomed Pharma GmbH) given as soon as possible after the first dose of adrenaline. Additional doses of vasopressin (20 IU) will be administered after each adrenaline dose for a maximum of four doses (80 IU). Vasopressin, Arginine: 20 IE of vasopressin per dose for a maximum of four doses (80 IU) Methylprednisolone: 40 mg methylprednisolone once	The placebo for vasopressin will consist of 1 mL of 9 mg/mL NaCl ("normal saline") from 2 mL ampules identical to the vasopressin ampules. The placebo for methylprednisolone will also consist of 1 mL of 9 mg/mL NaCl. NaCl: Placebo
Measure Participants	237	264
Count of Participants [Participants]	18 7.6%	20 7.6%

4. Other Pre-specified Outcome

Title	Vasopressor-free Days
Description	Vasopressor-free days will be defined as the number of days within the first 7 days after the cardiac arrest where the patient is not receiving vasopressors and is alive.
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

5. Other Pre-specified Outcome

Title	Invasive Ventilation-free Days
Description	Invasive ventilation-free days will be defined as the number of days within the first 7 days after the cardiac arrest where the patient is not receiving invasive ventilation and is alive.
Time Frame	7 days

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

6. Other Pre-specified Outcome

Title	Sequential Organ Failure Assessment (SOFA) Score at 24, 48 and 72 Hours
Description	The SOFA score is a validated and widely used measure of organ failure assessing the respiratory, nervous, cardiovascular, hepatic, coagulation, and renal systems. We will assess both the cardiovascular sub score as well as the overall SOFA score.
Time Frame	24, 48 and 72 hours

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

7. Other Pre-specified Outcome

Title	Hospital Disposition
Description	Hospital disposition (e.g. home, rehabilitation, nursing home, hospice) will be defined at the time of discharge from the initial acute care hospital.
Time Frame	At hospital discharge, up to 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

8. Other Pre-specified Outcome

Title	Survival
Time Frame	At 90 days, 180 days, and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

9. Other Pre-specified Outcome

Title	Favorable Neurological Outcome
Description	A favorable neurological outcome will be defined as a cerebral performance category score of 1 or 2. The cerebral performance category score is a 5-point scale assessing neurological/functional outcomes after brain damage with higher scores indicating worse neurological/functional outcomes.
Time Frame	At 90 days, 180 days, and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

10. Other Pre-specified Outcome

Title	Modified Rankin Scale (mRS)
Description	The mRS is a 7-point scale, ranging from 0 (no symptoms) to 6 (dead), assessing the degree of disability and dependence after a neurological injury such as stroke or cardiac arrest. A good outcome will be defined as a mRS of 0 to 3 and a poor outcome as 4 to 6.
Time Frame	At 30 days, 90 days, 180 days, and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

11. Other Pre-specified Outcome

Title	Glasgow Outcome Scale Extended (GOSE)
Description	The GOSE is a 8-point scale that is an extension of the Glasgow Outcomes Scale (which is identical to the CPC, only with inverse scores) where the scores 1, 2 and 3 from the CPC score is divided into two.
Time Frame	At 30 days, 90 days, 180 days, and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

12. Other Pre-specified Outcome

Title	Health-related Quality of Life (EQ-5D-5L)
Description	The EQ-5D-5L is a well-established measure of health-related quality of life that is quantified as a utility (i.e. a measure of quality of life between 0 and 1).
Time Frame	At 30 days, 90 days, 180 days, and 1 year

Outcome Measure Data

Analysis Population Description

[Not Specified]

Arm/Group Title

Arm/Group Description

Adverse Events

Time Frame	Through hospital admission up to 1 year
Arm/Group Title	Vasopressin and Methylprednisolone		Placebo
Arm/Group Description	The study drugs will consist of 40 mg methylprednisolone (Solu-medrol®, Pfizer) and 20 IU of vasopressin (Empressin®, Amomed Pharma GmbH) given as soon as possible after the first dose of adrenaline. Additional doses of vasopressin (20 IU) will be administered after each adrenaline dose for a maximum of four doses (80 IU). Vasopressin, Arginine: 20 IE of vasopressin per dose for a maximum of four doses (80 IU) Methylprednisolone: 40 mg methylprednisolone once		The placebo for vasopressin will consist of 1 mL of 9 mg/mL NaCl ("normal saline") from 2 mL ampules identical to the vasopressin ampules. The placebo for methylprednisolone will also consist of 1 mL of 9 mg/mL NaCl. NaCl: Placebo
All Cause Mortality
	Vasopressin and Methylprednisolone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	214/237 (90.3%)		233/264 (88.3%)
Serious Adverse Events
	Vasopressin and Methylprednisolone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/237 (0%)		0/264 (0%)
Other (Not Including Serious) Adverse Events
	Vasopressin and Methylprednisolone		Placebo
	Affected / at Risk (%)	# Events	Affected / at Risk (%)	# Events
Total	0/237 (0%)		0/264 (0%)

Limitations/Caveats

[Not Specified]

More Information

Certain Agreements

All Principal Investigators ARE 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.