Bicarbonate for In-Hospital Cardiac Arrest (BIHCA)

Bicarbonate 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 sodium bicarbonate during adult in-hospital cardiac arrest. There will be 22 enrolling sites in Denmark. 778 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: Recruiting
• Conditions: Cardiac Arrest
• Intervention / Treatment: Drug: Sodium bicarbonate; Drug: Sodium chloride

• Study Type: Interventional
• Enrollment (Estimated): 778
• Phase: Phase 4

Contacts and Locations

• Study Contact: Name: Lars W Andersen; Phone Number: +4551781511; Email: lwandersen@clin.au.dk
• Study Contact Backup: Name: Asger Granfeldt; Email: granfeldt@clin.au.dk

Study Locations

• Denmark
  • Aabenraa, Denmark, 6200
    • Recruiting
    • Hospital of Southern Jutland - Aabenraa
    • Contact: Jennifer Eskol
  • Aalborg, Denmark, 9000
    • Recruiting
    • Aalborg University Hospital
    • Contact: Signe Riddersholm
  • Aarhus, Denmark, 8000
    • Recruiting
    • Aarhus University Hospital
    • Contact: Asger Granfeldt
  • Bispebjerg, Denmark, 2400
    • Recruiting
    • Copenhagen University Hospital - Bispebjerg
    • Contact: Theis Itenov
  • Copenhagen, Denmark, 2100
    • Recruiting
    • Copenhagen University Hospital - Rigshospitalet
    • Contact: Dan Isbye
  • Esbjerg, Denmark, 6700
    • Recruiting
    • Hospital of Southwest Jutland - Esbjerg
    • Contact: Peter Qvist
  • Gentofte, Denmark, 2900
    • Recruiting
    • Copenhagen University Hospital - Gentofte
    • Contact: Fredrik Folke
  • Gødstrup, Denmark, 7400
    • Recruiting
    • Gødstrup Hospital
    • Contact: Rasmus Nielsen
  • Herlev, Denmark, 2730
    • Recruiting
    • Copenhagen University Hospital - Herlev
    • Contact: Kasper Iversen
  • Hjørring, Denmark, 9800
    • Recruiting
    • North Denmark Region Hospital - Hjørring
    • Contact: Andrei Ciubotariu
  • Holbæk, Denmark, 4300
    • Recruiting
    • Holbæk Hospital
    • Contact: Mette Krag
  • Horsens, Denmark, 8700
    • Recruiting
    • Horsens Regional Hospital
    • Contact: Ulrick Espelund
  • Hvidovre, Denmark, 2650
    • Recruiting
    • Hvidovre Hospital
    • Contact: Klaus Kristiansen
  • Kolding, Denmark, 6000
    • Recruiting
    • Kolding Hospital
    • Contact: Anne Brøchner
  • Køge, Denmark, 4600
    • Recruiting
    • Zealand University Hospital - Køge
    • Contact: Rikke Malene Jepsen
  • Nykøbing Falster, Denmark, 4800
    • Not yet recruiting
    • Nykøbing Falster Hospital
    • Contact: Ninna Holm
  • Odense, Denmark, 5000
    • Recruiting
    • Odense University Hospital
    • Contact: Søren Darling
  • Randers, Denmark, 8930
    • Not yet recruiting
    • Randers Regional Hospital
    • Contact: Bo Løfgren
  • Roskilde, Denmark, 4000
    • Recruiting
    • Zealand University Hospital - Roskilde
    • Contact: Camilla Asferg
  • Slagelse, Denmark, 4200
    • Recruiting
    • Slagelse Hospital
    • Contact: Morten Plambech
  • Svendborg, Denmark, 5700
    • Recruiting
    • Odense University Hospital - Svendborg
    • Contact: Peter Martin Hansen
  • Viborg, Denmark, 8800
    • Recruiting
    • Viborg Regional Hospital
    • Contact: Christoffer Sølling

Participation Criteria

Eligibility Criteria

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

Description

Inclusion Criteria:

1. In-hospital cardiac arrest
2. Age ≥ 18 years
3. Received at least one dose of adrenaline during cardiopulmonary resuscitation (CPR)

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
5. Known objection by the patient to participate in the trial
6. Clinical indication for bicarbonate administration

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: Sodium bicarbonate; 50 ml of 1 mmol/ml sodium bicarbonate given as soon as possible after the first dose of adrenaline. If the patient remains in cardiac arrest, one additional dose of 50 ml of 1 mmol/ml sodium bicarbonate will be administered after the second dose of adrenaline dose for a maximum of two doses.	Drug: Sodium bicarbonate; Sodium bicarbonate 1 mmol/ml
Placebo Comparator: Placebo; 50 mL of 9 mg/mL NaCl ("normal saline") given as soon as possible after the first dose of adrenaline. If the patient remains in cardiac arrest, one additional dose of 50 mL of 9 mg/mL NaCl will be administered after the second dose of adrenaline dose for a maximum of two doses.	Drug: Sodium chloride; Sodium chloride 9 mg/mL

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 modified Rankin Scale score of 0, 1, 2 or 3. The modified Rankin Scale is a 7-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
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
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
Favorable Neurological Outcome	A favorable neurological outcome will be defined as a modified Rankin Scale score of 0, 1, 2 or 3. The modified Rankin Scale is a 7-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
Cerebral performance category	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, 90 days, 180 days, and 1 year
Sequential Organ Failure Assessment (SOFA) Score	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.	At 2, 24, 48 and 72 hours
pH	Unit: None	Immediately after return of spontaneous circulation, often within 1 hour
Standard bicarbonate	Unit: mmol/L	Immediately after return of spontaneous circulation, often within 1 hour
pCO2	Partial pressure of CO2 in arterial blood. Unit: kPa	Immediately after return of spontaneous circulation, often within 1 hour
Potassium	Unit: mmol/L	Immediately after return of spontaneous circulation, often within 1 hour
Calcium	Unit: mmol/L	Immediately after return of spontaneous circulation, often within 1 hour
Sodium	Unit: mmol/L	Immediately after return of spontaneous circulation, often within 1 hour
Lactate	Unit: mmol/L	Immediately after return of spontaneous circulation, often within 1 hour

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): February 6, 2023
• Primary Completion (Estimated): May 28, 2025
• Study Completion (Estimated): February 1, 2026

Study Registration Dates

• First Submitted: September 27, 2022
• First Submitted That Met QC Criteria: September 30, 2022
• First Posted (Actual): October 3, 2022

Study Record Updates

• Last Update Posted (Estimated): October 10, 2023
• Last Update Submitted That Met QC Criteria: October 9, 2023
• Last Verified: October 1, 2023

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Heart Diseases; Cardiovascular Diseases; Heart Arrest
• Other Study ID Numbers: 00004

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; SAP; 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
• product manufactured in and exported from the U.S.: No