Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest (VAM-IHCA)

Vasopressin and Methylprednisolone for In-Hospital Cardiac Arrest - A Randomized, Double-Blind, Placebo-Controlled Trial

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.

Study Overview

• Status: Completed
• Conditions: Heart Arrest
• Intervention / Treatment: Drug: Vasopressin, Arginine; Drug: Methylprednisolone; Drug: NaCl

• Study Type: Interventional
• Enrollment (Actual): 501
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark
    • Aalborg University Hospital
  • Aarhus, Denmark
    • Aarhus University Hospital
  • Copenhagen, Denmark
    • Copenhagen University Hospital - Rigshospitalet
  • Hellerup, Denmark
    • Copenhagen University Hospital - Gentofte
  • Herlev, Denmark
    • Copenhagen University Hospital - Herlev
  • Horsens, Denmark
    • Horsens Regional Hospital
  • Køge, Denmark
    • Zealand University Hospital - Køge
  • Odense, Denmark
    • Odense University Hospital
  • Randers, Denmark
    • Randers Regional Hospital
  • Viborg, Denmark
    • Viborg Regional Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Quadruple

Number of Arms

2

Arms and Interventions

Participant Group / 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

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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	During the cardiac arrest, an average of 20 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants That Survived 30 Days		At 30 days
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.	At 30 days

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
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.	7 days
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.	7 days
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.	24, 48 and 72 hours
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.	At hospital discharge, up to 1 year
Survival		At 90 days, 180 days, and 1 year
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.	At 90 days, 180 days, and 1 year
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.	At 30 days, 90 days, 180 days, and 1 year
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.	At 30 days, 90 days, 180 days, and 1 year
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).	At 30 days, 90 days, 180 days, and 1 year

Collaborators and Investigators

• Sponsor: Lars Wiuff Andersen
• Collaborators: University of Aarhus
• Investigators: Principal Investigator: Lars W Andersen, MD, MPH, PhD, DMSc, Aarhus University Hospital

Publications and helpful links

General Publications

• Andersen LW, Isbye D, Kjaergaard J, Kristensen CM, Darling S, Zwisler ST, Fisker S, Schmidt JC, Kirkegaard H, Grejs AM, Rossau JRG, Larsen JM, Rasmussen BS, Riddersholm S, Iversen K, Schultz M, Nielsen JL, Lofgren B, Lauridsen KG, Solling C, Paelestik K, Kjaergaard AG, Due-Rasmussen D, Folke F, Charlot MG, Jepsen RMHG, Wiberg S, Donnino M, Kurth T, Hoybye M, Sindberg B, Holmberg MJ, Granfeldt A. Effect of Vasopressin and Methylprednisolone vs Placebo on Return of Spontaneous Circulation in Patients With In-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA. 2021 Oct 26;326(16):1586-1594. doi: 10.1001/jama.2021.16628.
• Andersen LW, Sindberg B, Holmberg M, Isbye D, Kjærgaard J, Zwisler ST, Darling S, Larsen JM, Rasmussen BS, Løfgren B, Lauridsen KG, Pælestik KB, Sølling C, Kjærgaard AG, Due-Rasmussen D, Folke F, Charlot MG, Iversen K, Schultz M, Wiberg S, Jepsen RMHG, Kurth T, Donnino M, Kirkegaard H, Granfeldt A. Vasopressin and methylprednisolone for in-hospital cardiac arrest - Protocol for a randomized, double-blind, placebo-controlled trial. Resusc Plus. 2021 Jan 30;5:100081. doi: 10.1016/j.resplu.2021.100081. eCollection 2021 Mar.

Helpful Links

• Trial website

Study record dates

Study Major Dates

• Study Start (Actual): September 17, 2018
• Primary Completion (Actual): January 21, 2021
• Study Completion (Actual): January 21, 2022

Study Registration Dates

• First Submitted: August 19, 2018
• First Submitted That Met QC Criteria: August 19, 2018
• First Posted (Actual): August 21, 2018

Study Record Updates

• Last Update Posted (Actual): March 2, 2022
• Last Update Submitted That Met QC Criteria: February 17, 2022
• Last Verified: February 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Arrest; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Neuroprotective Agents; Protective Agents; Natriuretic Agents; Hemostatics; Coagulants; Vasoconstrictor Agents; Antidiuretic Agents; Methylprednisolone; Vasopressins; Arginine Vasopressin
• Other Study ID Numbers: 00001; 2017-004773-13 (EudraCT Number)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Yes

IPD Plan Description

Six months after the publication of the last results, all de-identified individual patient data will be made available for data sharing. Procedures, including re-coding of key variables, will be put in place to allow for complete de-identification of the data. Data will be completely anonymized according to Danish law.

All relevant trial-related documents, including the protocol, data dictionary, and the main statistical code, will be shared along with the data. There will be no predetermined end date for the data sharing.

• IPD Sharing Access Criteria: Data will be available for any research purpose to all interested parties who have approval from an independent review committee and who have a methodological sound proposal as determined by the steering committee of the current trial. Only the methodological qualities and not the purpose or objective of the proposal will be considered. Interested parties will be able to request the data by contacting the principal investigator. Authorship of publications emerging from the shared data will follow standard authorship guidelines from the International Committee of Medical Journal Editors and might or might not include authors from the steering committee depending on the nature of their involvement.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No