52 in 52 – #9: The COCA Trial

Welcome back to the “52 in 52” series. This collection of posts features recently published must-know articles. Our ninth post looks at the COCA trial.

Author: Brannon Inman (Chief Resident, Emergency Medicine Physician, San Antonio, TX) // Reviewed by: Alex Koyfman, MD (@EMHighAK); Brit Long, MD (@long_brit)

AKA:  THE “COCA” TRIAL

Clinical question:

In patients with out-of-hospital cardiac arrest, does the administration of calcium lead to more ROSC?

Study design:

• Double blind, parallel group, superiority, randomized placebo-controlled trial

PICO:

Population:

• Included patients > 18 years in Denmark with out of hospital cardiac arrest
• Must have received 1 mg epinephrine
• Exclusion
  • Traumatic cardiac arrest
  • Known or suspected pregnancy
  • Prior enrollment in the trial
  • Receipt of epinephrine outside the trial (i.e. from an EMS not participating in the trial)
  • Clinical indication for calcium (hypocalcemia or hyperkalemia)
• 391 patients included in analysis, mean age 68 years, male 71%/female 29%, 75% with initial nonshockable rhythm, 82% cardiac arrest at home

Intervention:

• Calcium IV or IO x 2 doses (5 mmol or 200 mg of calcium chloride), first dose administered right after first dose of epinephrine
• Median time to study drug administration of 18 minutes
• IO access in 60%

Comparator:

• Administration of equitable volume of normal saline

Outcome:

• Primary outcome: Sustained ROSC for at least 20 minutes
  • 19% in calcium group vs 27% in placebo group
  • Risk ratio: 0.72 [95% CI, 0.49 to 1.03]
• Secondary outcome
  • Survival at 30 days: 5.2% vs. 9.1%, RR 0.57 (95% CI -9.4 to 1.3)
  • Favorable neurologic outcome at 30 days: 3.6% vs. 7.6%, RR 0.48 (95% CI 0.20 to 1.12)
  • Hypercalcemia: Calcium group 74%, NS group 2%
• Trial stopped early due to suggested harm in the calcium group

Take away:

• Trial stopped early due to suggested harm
• The trial asks a clinically important question, but it uses a surrogate outcome (ROSC for at least 20 minutes). Patient centered outcomes were secondary.
• The study was stopped early which can overestimate harms. This also increases the risk that the results are due to random chance.
• Overall this was a well conducted study, with no loss to follow up rate and few protocol deviations.
• Authors did demonstrate that calcium administration increased calcium levels.
• It took about 18 minutes to administer the study drug. It is possible calcium may be helpful if given early, but in all comers with OHCA, calcium is not warranted.
• Few patients had shockable rhythms initially.
• Hyperkalemia patients may receive the most benefit from calcium, but these patients were not included.

My take:

In all-comers with OHCA I won’t be giving calcium based on this trial. However, in trauma patients and those in whom I suspect hyperkalemia, calcium channel blocker overdose, or hypocalcemia, I absolutely will.

Reference:

1. Vallentin MF, Granfeldt A, Meilandt C, et al. 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;326(22):2268-2276. doi:10.1001/jama.2021.20929