Calcium for Out-of-Hospital Cardiac Arrest (COCA)

Calcium for Out-of-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 calcium during adult out-of-hospital cardiac arrest. 430 adult patients with out-of-hospital cardiac arrest receiving at least one dose of adrenaline will be enrolled. The primary outcome is sustained 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, Out-Of-Hospital
• Intervention / Treatment: Drug: Calcium Chloride; Drug: Sodium chloride 0.9%

• Study Type: Interventional
• Enrollment (Actual): 397
• Phase: Phase 2

Contacts and Locations

Study Locations

• Denmark
  • Central Denmark Region
    • Aarhus N, Central Denmark Region, Denmark, 8200
      • Prehospital Emergency Medical Services

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Out-of-hospital cardiac arrest
• Age ≥ 18 years
• Received at least one dose of adrenaline

Exclusion Criteria:

• Traumatic cardiac arrest - including drowning and external asphyxia (e.g., hanging, strangulation, or foreign object airway obstruction)
• Known or strongly suspected pregnancy
• Prior enrollment in the trial
• Received adrenaline during cardiac arrest before arrival of prehospital personnel with the study drug
• Clinical indication for calcium administration during 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: Calcium; The intervention will consist of 5 mmol (10 mL ampoule) of calcium chloride (CaCl2) administered intravenously or intraosseously immediately after the first dose of adrenaline and again after the second dose of adrenaline.	Drug: Calcium Chloride; Calcium chloride 5 mmol; Other Names: CaCl2
Placebo Comparator: Placebo; The placebo will consist of 10 mL of 9 mg/mL sodium chloride (NaCl, "normal saline") administered intravenously or intraosseously immediately after the first dose of adrenaline and again after the second dose of adrenaline.	Drug: Sodium chloride 0.9%; Placebo

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With Sustained Return of Spontaneous Circulation	Palpable pulses or other signs of circulation without a need for chest compressions lasting at least 20 minutes.	Before or after hospital arrival (up to 2 hours after the cardiac arrest)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Number of Participants With 30-day Survival		30 days after the cardiac arrest
Number of Participants With 30-day Favorable Neurological Outcome	Neurological outcome will be assessed with the modified Rankin Scale (mRS) which is a scale from 0 to 6 assessing neurological/functional outcomes after brain damage with higher scores indicating worse neurological/functional outcomes. The scale will will be dichotomized as favorable (mRS 0-3) vs. unfavorable (mRS 4-6).	30 days after the cardiac arrest

Collaborators and Investigators

• Sponsor: Lars Wiuff Andersen
• Collaborators: University of Aarhus; Central Denmark Region

Publications and helpful links

General Publications

• Vallentin MF, Granfeldt A, Meilandt C, Povlsen AL, Sindberg B, Holmberg MJ, Iversen BN, Maerkedahl R, Mortensen LR, Nyboe R, Vandborg MP, Tarpgaard M, Runge C, Christiansen CF, Dissing TH, Terkelsen CJ, Christensen S, Kirkegaard H, Andersen LW. Effect of calcium vs. placebo on long-term outcomes in patients with out-of-hospital cardiac arrest. Resuscitation. 2022 Oct;179:21-24. doi: 10.1016/j.resuscitation.2022.07.034. Epub 2022 Jul 30.
• Vallentin MF, Granfeldt A, Meilandt C, Povlsen AL, Sindberg B, Holmberg MJ, Iversen BN, Maerkedahl R, Mortensen LR, Nyboe R, Vandborg MP, Tarpgaard M, Runge C, Christiansen CF, Dissing TH, Terkelsen CJ, Christensen S, Kirkegaard H, Andersen LW. Effect of Intravenous or Intraosseous Calcium vs Saline on Return of Spontaneous Circulation in Adults With Out-of-Hospital Cardiac Arrest: A Randomized Clinical Trial. JAMA. 2021 Dec 14;326(22):2268-2276. doi: 10.1001/jama.2021.20929.

Helpful Links

• Trial website

Study record dates

Study Major Dates

• Study Start (Actual): January 20, 2020
• Primary Completion (Actual): April 15, 2021
• Study Completion (Actual): April 15, 2022

Study Registration Dates

• First Submitted: November 3, 2019
• First Submitted That Met QC Criteria: November 5, 2019
• First Posted (Actual): November 6, 2019

Study Record Updates

• Last Update Posted (Actual): July 25, 2022
• Last Update Submitted That Met QC Criteria: July 18, 2022
• Last Verified: July 1, 2022

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Arrest; Out-of-Hospital Cardiac Arrest; Physiological Effects of Drugs; Calcium-Regulating Hormones and Agents; Calcium
• Other Study ID Numbers: 00002; 2019-003387-46 (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 deidentified 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 deidentification of the data. Data will be completely anonymized according to Danish law.
• IPD Sharing Time Frame: Six months after the publication of the last results
• 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.
• IPD Sharing Supporting Information Type: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Analytic Code

Drug and device information, study documents

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