Heart Arrest
Conditions
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.
Interventions
20 IE of vasopressin per dose for a maximum of four doses (80 IU)
DRUGMethylprednisolone
40 mg methylprednisolone once
DRUGNaCl
Placebo
Sponsors
University of Aarhus
Lars Wiuff Andersen
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
QUADRUPLE (Subject, Caregiver, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to No maximum
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
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| 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
| Measure | Time frame | Description |
|---|---|---|
| Number of Participants That Survived 30 Days | At 30 days | — |
| 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
| Measure | Time frame | Description |
|---|---|---|
| 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. |
| Survival | At 90 days, 180 days, and 1 year | — |
| 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. |
| 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. |
| 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. |
| 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). |
| 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. |
| 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. |
| 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. |
Countries
Denmark
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| 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).
Vasopressin, Arginine: 20 IE of vasopressin per dose for a maximum of four doses (80 IU)
Methylprednisolone: 40 mg methylprednisolone once | 237 |
| 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.
NaCl: Placebo | 264 |
| Total | 501 |
Baseline characteristics
| Characteristic | Vasopressin and Methylprednisolone | Placebo | Total |
|---|---|---|---|
| Age, Continuous | 71 years STANDARD_DEVIATION 13 | 70 years STANDARD_DEVIATION 12 | 71 years STANDARD_DEVIATION 13 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 89 Participants | 90 Participants | 179 Participants |
| Sex: Female, Male Male | 148 Participants | 174 Participants | 322 Participants |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 214 / 237 | 233 / 264 |
| other Total, other adverse events | 0 / 237 | 0 / 264 |
| serious Total, serious adverse events | 0 / 237 | 0 / 264 |
Outcome results
Primary
Number of Participants With Return of Spontaneous Circulation
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
| Arm | Measure | Value (NUMBER) |
|---|---|---|
| Vasopressin and Methylprednisolone | Number of Participants With Return of Spontaneous Circulation | 100 participants |
| Placebo | Number of Participants With Return of Spontaneous Circulation | 86 participants |
Secondary
Number of Participants That Survived 30 Days
Time frame: At 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vasopressin and Methylprednisolone | Number of Participants That Survived 30 Days | 23 Participants |
| Placebo | Number of Participants That Survived 30 Days | 31 Participants |
Secondary
Number of Participants With a Favorable Neurological Outcome 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.
Time frame: At 30 days
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Vasopressin and Methylprednisolone | Number of Participants With a Favorable Neurological Outcome at 30 Days | 18 Participants |
| Placebo | Number of Participants With a Favorable Neurological Outcome at 30 Days | 20 Participants |
Other Pre-specified
Favorable Neurological Outcome
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
Other Pre-specified
Glasgow Outcome Scale Extended (GOSE)
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
Other Pre-specified
Health-related Quality of Life (EQ-5D-5L)
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
Other Pre-specified
Hospital Disposition
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
Other Pre-specified
Invasive Ventilation-free 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.
Time frame: 7 days
Other Pre-specified
Modified Rankin Scale (mRS)
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
Other Pre-specified
Sequential Organ Failure Assessment (SOFA) Score at 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.
Time frame: 24, 48 and 72 hours
Other Pre-specified
Survival
Time frame: At 90 days, 180 days, and 1 year
Other Pre-specified
Vasopressor-free 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.
Time frame: 7 days