Clinical Trial Results:
Calcium for Out-of-Hospital Cardiac Arrest – A Randomized, Double-Blind, Placebo-Controlled trial
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Summary
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EudraCT number |
2019-003387-46 |
Trial protocol |
DK |
Global end of trial date |
16 Apr 2021
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Results information
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Results version number |
v1(current) |
This version publication date |
10 Sep 2022
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First version publication date |
10 Sep 2022
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Other versions |
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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 |
COCA2
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Additional study identifiers
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ISRCTN number |
- | ||
US NCT number |
NCT04153435 | ||
WHO universal trial number (UTN) |
- | ||
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Sponsors
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Sponsor organisation name |
Prehospital Emergency Medical Services: Central Denmark Region
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Sponsor organisation address |
Olof Palmes Allé 34, 1., Aarhus N, Denmark, DK-8200
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Public contact |
Lars Wiuff Andersen, Research Center for Emergency Medicine Department of Clinical Medicine Aarhus University, 0045 51781511, lwandersen@clin.au.dk
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Scientific contact |
Lars Wiuff Andersen, 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 |
Final
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Date of interim/final analysis |
30 Nov 2021
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Is this the analysis of the primary completion data? |
Yes
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Primary completion date |
16 Apr 2021
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Global end of trial reached? |
Yes
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Global end of trial date |
16 Apr 2021
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Was the trial ended prematurely? |
Yes
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General information about the trial
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Main objective of the trial |
To determine whether calcium administration during adult OHCA will improve 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 |
20 Jan 2020
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Long term follow-up planned |
Yes
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Long term follow-up rationale |
Ethical reason, Scientific research, Efficacy | ||
Long term follow-up duration |
12 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: 391
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Worldwide total number of subjects |
391
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EEA total number of subjects |
391
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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) |
131
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From 65 to 84 years |
231
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85 years and over |
29
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Recruitment
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Recruitment details |
Patients were screened through dispatch logs, prehospital journals, and clinican reports Patients were included by the prehospital personnel by administrating at least one dose of the trial drug when the patient met the criteria for inclusion | |||||||||
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Pre-assignment
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Screening details |
1221 patients had an out-of-hospital cardiac arrest in the Central Denmark Region during the inclusion time frame --- 830 Excluded 578 Did not meet inclusion criteria 63 Met exclusion criteria 189 Excluded for other reasons | |||||||||
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Period 1
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Period 1 title |
Jan 20, 2020 - Apr 16, 2021 (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, Carer, 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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Intervention | |||||||||
Arm description |
- | |||||||||
Arm type |
Experimental | |||||||||
Investigational medicinal product name |
Calciumchlorid ”SAD” injektionsvæske, opløsning
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Investigational medicinal product code |
A 12 AA 07
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Other name |
Calcium chloride
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Pharmaceutical forms |
Solution for injection
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Routes of administration |
Intraosseous use, Intravenous use
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Dosage and administration details |
Calcium chloride (0.5 mmol/mL) 10 mL per dose - maximum of two doses
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Arm title
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Placebo | |||||||||
Arm description |
- | |||||||||
Arm type |
Placebo | |||||||||
Investigational medicinal product name |
Sodium chloride 0.9%
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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 |
Intraosseous use, Intravenous use
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Dosage and administration details |
Sodium Chloride 0.9% - 10 mL per dose - maximum of 2 doses
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Baseline characteristics reporting groups
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Reporting group title |
Intervention
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo
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Reporting group description |
- | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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End points reporting groups
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Reporting group title |
Intervention
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Reporting group description |
- | ||
Reporting group title |
Placebo
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Reporting group description |
- | ||
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End point title |
Return of spontaneous circulation | |||||||||
End point description |
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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End point type |
Primary
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End point timeframe |
Patient either achieved the primary outcome or died
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Statistical analysis title |
Return of spontaneous circulation | |||||||||
Comparison groups |
Intervention v Placebo
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Number of subjects included in analysis |
391
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.09 | |||||||||
Method |
Fisher exact | |||||||||
Parameter type |
Mean difference (final values) | |||||||||
Point estimate |
-7.6
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
-16 | |||||||||
upper limit |
0.8 | |||||||||
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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 |
30 days after the cardiac arrest occurred
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Statistical analysis title |
Survival at 30 days | |||||||||
Comparison groups |
Intervention v Placebo
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Number of subjects included in analysis |
391
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.17 | |||||||||
Method |
Fisher exact | |||||||||
Parameter type |
Mean difference (final values) | |||||||||
Point estimate |
-3.9
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
-9.4 | |||||||||
upper limit |
1.3 | |||||||||
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End point title |
Survival at 30 days with a favorable neurological outcome | |||||||||
End point description |
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End point type |
Secondary
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End point timeframe |
30 days after the cardiac arrest occurred
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Statistical analysis title |
Survival at 30 days with a favorable neurological | |||||||||
Comparison groups |
Intervention v Placebo
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Number of subjects included in analysis |
391
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Analysis specification |
Pre-specified
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Analysis type |
superiority | |||||||||
P-value |
= 0.12 | |||||||||
Method |
Fisher exact | |||||||||
Parameter type |
Mean difference (final values) | |||||||||
Point estimate |
-4
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Confidence interval |
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level |
95% | |||||||||
sides |
2-sided
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lower limit |
-8.9 | |||||||||
upper limit |
0.7 | |||||||||
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Adverse events information
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Timeframe for reporting adverse events |
Jan 20, 2020 - Apr 16, 2021
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Assessment type |
Systematic | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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Dictionary used for adverse event reporting
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Dictionary name |
Data Dictionary | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Dictionary version |
1.4
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Reporting groups
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Reporting group title |
Intervention (achieved ROSC)
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Reporting group description |
Specific adverse events were only entered for patients who achieved ROSC - please see protocol for details | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Reporting group title |
Placebo (achieved ROSC)
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Reporting group description |
Specific adverse events were only entered for patients who achieved ROSC - please see protocol for details | ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
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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? Yes | |||||||
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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. | |||||||
| 1) Trial was stopped early leading to risk of overestimating effect size, 2) The trial only tested one dosing regime and timing, 3) The generalizability to the in-hospital setting is unclear | |||||||
Online references |
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| http://www.ncbi.nlm.nih.gov/pubmed/35917866 http://www.ncbi.nlm.nih.gov/pubmed/34847226 |
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