Clinical Trial Results:
Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest – A Randomized, Double-Blind, Placebo-Controlled Trial
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Summary
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EudraCT number |
2017-004773-13 |
Trial protocol |
DK |
Global end of trial date |
21 Jan 2022
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Results information
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Results version number |
v2(current) |
This version publication date |
06 May 2022
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First version publication date |
17 Nov 2021
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Other versions |
v1 |
Version creation reason |
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Trial Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
Subject Disposition
Baseline Characteristics
End Points
Adverse Events
More Information
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Trial identification
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Sponsor protocol code |
00001
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT03640949 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Aarhus University Hospital
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Sponsor organisation address |
Palle Juul Jensens blvd 99, Aarhus, Denmark, 8200
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Public contact |
Research Center for Emergency Medic, Research Center for Emergency Medicine Department of Clinical Medicine Aarhus University , 0045 51781511, lwandersen@clin.au.dk
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Scientific contact |
Research Center for Emergency Medic, Research Center for Emergency Medicine Department of Clinical Medicine Aarhus University , 0045 51781511, lwandersen@clin.au.dk
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Paediatric regulatory details
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Is trial part of an agreed paediatric investigation plan (PIP) |
No
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Does article 45 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Does article 46 of REGULATION (EC) No 1901/2006 apply to this trial? |
No
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Results analysis stage
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Analysis stage |
Interim
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Date of interim/final analysis |
22 Apr 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
21 Apr 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
21 Jan 2022
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Was the trial ended prematurely? |
No
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General information about the trial
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Main objective of the trial |
The primary objective of the study is to determine whether the combination of vasopressin and methylprednisolone, as compared to placebo, when administered during IHCA, will increase return of spontaneous circulation.
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Protection of trial subjects |
The study was approved by the regional ethics committee and the Danish Medicines Agency. An independent data monitoring committee oversaw the trial.
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Background therapy |
- | ||
Evidence for comparator |
- | ||
Actual start date of recruitment |
15 Oct 2018
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Efficacy, Ethical reason, Scientific research | ||
Long term follow-up duration |
3 Months | ||
Independent data monitoring committee (IDMC) involvement? |
Yes
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Population of trial subjects
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Number of subjects enrolled per country |
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Country: Number of subjects enrolled |
Denmark: 501
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Worldwide total number of subjects |
501
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EEA total number of subjects |
501
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Number of subjects enrolled per age group |
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In utero |
0
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Preterm newborn - gestational age < 37 wk |
0
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Newborns (0-27 days) |
0
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Infants and toddlers (28 days-23 months) |
0
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Children (2-11 years) |
0
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Adolescents (12-17 years) |
0
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Adults (18-64 years) |
126
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From 65 to 84 years |
327
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85 years and over |
48
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Recruitment
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Recruitment details |
- | |||||||||
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Pre-assignment
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Screening details |
2362 Patients with in-hospital cardiac arrest were screened for enrollment 1850 Excluded 685 Did not meet inclusion criteria 110 Met exclusion criteria 1055 Excluded for other reasons | |||||||||
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Period 1
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Period 1 title |
Overall trial (overall period)
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Is this the baseline period? |
Yes | |||||||||
Allocation method |
Randomised - controlled
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Blinding used |
Double blind | |||||||||
Roles blinded |
Subject, Investigator, Monitor, Data analyst, Assessor | |||||||||
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Arms
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Are arms mutually exclusive |
Yes
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Arm title
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Placebo | |||||||||
Arm description |
Placebo 9% saline | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Saline
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intravascular use
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Dosage and administration details |
Placebo consisted of 9 mg/mL of sodium chloride from identical ampoules
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Arm title
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Metylprednisolone and vasopressin | |||||||||
Arm description |
metylprednisolone and vasopressin | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Empressin®
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Solution for solution for infusion
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Routes of administration |
Intravascular use
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Dosage and administration details |
20 IU of vasopressin (Empressin, Amomed Pharma GmbH) given as soon as possible after the first dose of epinephrine. Additional doses of vasopressin (20 IU) were administered after each epinephrine dose for a
maximum of 4 doses (80 IU).
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Investigational medicinal product name |
SOLU-MEDROL®
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Investigational medicinal product code |
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Other name |
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Pharmaceutical forms |
Powder and solvent for solution for injection
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Routes of administration |
Intravascular use
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Dosage and administration details |
Solu-medrol® will be administered as a single dose of 40mg as soon as possible after the first dose of adrenaline.
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Baseline characteristics reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Placebo 9% saline | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Metylprednisolone and vasopressin
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Reporting group description |
metylprednisolone and vasopressin | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Placebo
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Reporting group description |
Placebo 9% saline | ||
Reporting group title |
Metylprednisolone and vasopressin
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Reporting group description |
metylprednisolone and vasopressin | ||
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End point title |
Return of spontaneous circulation | |||||||||
End point description |
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End point type |
Primary
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End point timeframe |
The primary outcome was return of spontaneous circulation, which was defined as spontaneous circulation with no further need for chest compressions sustained for at least
20 minutes
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Statistical analysis title |
Fisher exact test | |||||||||
Comparison groups |
Placebo v Metylprednisolone and vasopressin
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Number of subjects included in analysis |
501
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.03 | |||||||||
Method |
Fisher exact | |||||||||
Parameter type |
Mean difference (final values) | |||||||||
Point estimate |
9.6
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
1.1 | |||||||||
upper limit |
18 | |||||||||
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End point title |
Survival at 30 days with a favorable neurologic outcome | |||||||||
End point description |
favorable neurologic outcome, is defined as a Cerebral Performance Category score of 1 or 2. The Cerebral Performance Category score is a 5-point scale assessing neurologic outcomes after brain damage,
with higher scores indicating worse outcomes.
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End point type |
Secondary
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End point timeframe |
30 days
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Statistical analysis title |
Fisher exact test | |||||||||
Comparison groups |
Metylprednisolone and vasopressin v Placebo
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Number of subjects included in analysis |
501
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
> 0.99 | |||||||||
Method |
Fisher exact | |||||||||
Confidence interval |
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End point title |
Survival at 30 days | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
Survival at 30 days
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Statistical analysis title |
Fisher exact test | |||||||||
Comparison groups |
Placebo v Metylprednisolone and vasopressin
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Number of subjects included in analysis |
501
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.48 | |||||||||
Method |
Fisher exact | |||||||||
Confidence interval |
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Adverse events information
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Timeframe for reporting adverse events |
During admission
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Adverse event reporting additional description |
Definitions for adverse events are provided in the protocol. Hyperglycemia and hypernatremia were assessed within 48 hours after return of spontaneous circulation. The remainder of the
adverse events were assessed until death or hospital discharge.
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
Predefined in proto | ||||||||||||||||||||||||||||||
Dictionary version |
1
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Reporting groups
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Reporting group title |
Vasopressin and methylprednisolone
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Reporting group description |
- | ||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||
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| Frequency threshold for reporting non-serious adverse events: 0% | |||||||||||||||||||||||||||||||
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Substantial protocol amendments (globally) |
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| Were there any global substantial amendments to the protocol? No | |||
Interruptions (globally) |
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| Were there any global interruptions to the trial? No | |||
Limitations and caveats |
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| Limitations of the trial such as small numbers of subjects analysed or technical problems leading to unreliable data. | |||
| None reported | |||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/34587236 http://www.ncbi.nlm.nih.gov/pubmed/34223347 |
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