High Calcium Crystalloid Therapy for Cardiac Arrest

(SPEAR Trial)

Recruiting in Palo Alto (17 mi)

Overseen by Carol Bernier, DO

Age: 18+

Sex: Any

Travel: May Be Covered

Time Reimbursement: Varies

Trial Phase: Phase 2 & 3

Recruiting

Sponsor: Carol Bernier

Must not be taking: Digitalis

Disqualifiers: Under 18, Pregnancy, DNR, others

No Placebo Group

Prior Safety Data

Approved in 1 Jurisdiction

Trial Summary

What is the purpose of this trial?

The Carilion Clinic and Virginia Tech Carilion School of Medicine, in conjunction with Roanoke Fire-EMS, Botetourt County Department of Fire \& EMS and Salem Fire-EMS, are studying the outcomes of patients experiencing Pulseless Electrical Activity (PEA). PEA refers to a type of cardiac arrest in which there is normal electrical activity in the heart however the heart still fails to contract to generate a pulse. Without heart contractions, which normally generates a pulse, the brain and other important organs fail to receive blood and oxygen. Unfortunately, the majority (97.3%) of patients that experience this rhythm do not survive and most don't even make it to the hospital. This study is trying to determine if the administration of a High Calcium, Low Sodium (HCLS) fluid in pre-hospital care will improve the chances of survival. Generally, a sodium (salt) solution is provided to patients experiencing cardiac arrest. Studies have shown that lower sodium and higher calcium content may activate certain parts of the heart cells required to generate a pulse under PEA conditions. This study is a double-blind, prospective, clinical trial. PEA patients will randomly receive either routine fluid therapy (salt solution) or a HCLS solution. While HCLS solution is not the standard fluid used by EMS providers responding to PEA, it is composed of FDA approved components and is occasionally used by EMS providers at their discretion in treating PEA. It is predicted that HCLS will either improve PEA survival or deliver similar outcomes as routine treatment. All patients will receive standard, high quality cardiac arrest and post-cardiac arrest care regardless of assigned treatment group.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications.

What data supports the effectiveness of the treatment High Calcium, Low Sodium Crystalloid Therapy for cardiac arrest?

There is no evidence that administering calcium during cardiopulmonary resuscitation improves survival from cardiac arrest. Calcium has been used in specific conditions like hyperkalemia (high potassium levels) and hypocalcemia (low calcium levels), but its role in cardiac arrest remains unclear due to limited evidence. ^{1 2 3 4 5}

Is High Calcium Crystalloid Therapy safe for humans?

High levels of calcium can be harmful to the heart, potentially causing irregular heartbeats or cardiac arrest. Studies have shown that using calcium during cardiac arrest does not improve survival rates, and there are reports of dangerously high calcium levels in the blood after treatment. ^{1 3 6 7 8}

How is High Calcium, Low Sodium Crystalloid Therapy different from other treatments for cardiac arrest?

High Calcium, Low Sodium Crystalloid Therapy is unique because it focuses on using a solution with high calcium and low sodium levels, which is different from standard treatments that do not typically adjust these specific electrolyte levels. This approach is novel as it aims to enhance myocardial protection during cardiac arrest, although the effectiveness of calcium in improving survival rates during cardiac arrest is still unclear based on existing studies. ^{1 2 3 7 9}

Eligibility Criteria

The SPEAR study is for patients who experience a type of cardiac arrest called PEA, where the heart's electrical activity is normal but it doesn't contract. Participants must be treated by certain EMS providers in Roanoke and not have a DNR order, known pregnancy, untreated cardiac arrest over 30 minutes, traumatic cardiac arrest, LVAD device or digitalis toxicity.

Inclusion Criteria

I was unconscious and had no pulse but my heart wasn't in a common irregular rhythm.

Exclusion Criteria

I may have side effects from heart medication.

I experienced a heart stoppage for over 30 minutes without treatment.

I have a DNR order and do not wish to be enrolled in the trial.

Trial Timeline

Screening

Participants are screened for eligibility to participate in the trial

Immediate

Treatment

Patients receive either routine fluid therapy (normal saline) or a High Calcium, Low Sodium (HCLS) solution during pre-hospital care

Up to 1 hour

Follow-up

Participants are monitored for neurological outcomes and survival to hospital discharge

Up to 30 days

Treatment Details

Interventions

• High Calcium, Low Sodium (HCLS) Crystalloid Therapy (Crystalloid Therapy)

Trial Overview This trial tests if High Calcium, Low Sodium (HCLS) fluid improves survival in PEA compared to standard salt solution therapy. It's a double-blind study meaning neither the patient nor provider knows which treatment is given. Patients are randomly assigned to receive either HCLS or routine fluid therapy.

Participant Groups

Group I: High-Calcium, Low- Sodium (HCLS) group Experimental Treatment 1 Intervention

Patients will receive a drip of blinded, intravenous, half-normal saline and an unblinded, intravenous, one gram bolus of calcium chloride.

Group II: High-Calcium, High- Sodium (HCHS) group Active Control 1 Intervention

Patients will receive a drip of blinded, intravenous, normal saline and an unblinded, intravenous, one gram bolus of calcium chloride.

High Calcium, Low Sodium (HCLS) Crystalloid Therapy is already approved in United States for the following indications:

🇺🇸 Approved in United States as High Calcium, Low Sodium Crystalloid Therapy for:

• Pulseless Electrical Activity (PEA) in cardiac arrest

Find a Clinic Near You

Research Locations Nearby Select from list below to view details:

Carilion Clinic Roanoke, VA

Who Is Running the Clinical Trial?

Carol Bernier Lead Sponsor

Virginia Polytechnic Institute and State University Collaborator

References

1. England pubmed.ncbi.nlm.nih.gov

Calcium administration during cardiac arrest: a systematic review. [2018] This topic highlights the results of the literature review on calcium therapy during cardiac arrest and cardiopulmonary resuscitation according to the Patient/population, Intervention, Comparator, Outcome structure. Eligible studies were assigned to one of the five levels of evidence. Their quality was rated as either good, fair, or poor and then classified as supportive, neutral, or opposing according to the outcome benefits. Among the 48 articles retrieved, 10 articles fulfilled all the criteria for analysis for the Guidelines preparation. There is no evidence that the administration of calcium during cardiopulmonary resuscitation improves survival from cardiac arrest irrespective of the presenting rhythm. In the setting of hyperkalemia, calcium channel blocker intoxication, hypocalcemia, and hypermagnesemia, the role of calcium remains unclear because of the limited amount of evidence. The main limitation is the scarcity of data, most of which relate to anoxic cardiac arrest, accounting for no more than 25% of the causes of cardiac arrest in humans.

2. Ireland pubmed.ncbi.nlm.nih.gov

Effect of calcium vs. placebo on long-term outcomes in patients with out-of-hospital cardiac arrest. [2022] The Calcium for Out-of-hospital Cardiac Arrest (COCA) trial was a randomized, placebo-controlled, double-blind trial of calcium for out-of-hospital cardiac arrest. The primary and secondary outcomes have been reported previously. This article describes the long-term outcomes of the trial.

3. United States pubmed.ncbi.nlm.nih.gov

Calcium: limited indications, some danger. [2013] Calcium chloride has been advocated since the 1920s for the resuscitation of asystole, electromechanical dissociation (EMD), and ventricular fibrillation. Reports of side effects and complications have been numerous. Studies of calcium assays following American Heart Association recommended dosages have shown dangerously elevated serum levels. Large retrospective clinical studies in Milwaukee and Tampa have found no evidence of improved survival with calcium chloride in asystole and EMD. A prospective randomized double-blind study comparing calcium chloride and saline controls in the Milwaukee Paramedic system for asystole and EMD using standard AHA protocols showed no statistically significant difference in resuscitation rates or long-term survival between the calcium and no-calcium groups for the rhythm of asystole. Although patients with EMD had statistically improved resuscitation rates when calcium chloride was given, only one of the patients survived to hospital discharge. Because of the low rates of resuscitation and long-term survival in patients presenting in asystole and EMD, proving that calcium chloride does not enhance survival would require large multicenter trials. However, since no controlled study has ever documented significant benefit, its routine use in asystole and EMD cannot be supported. Calcium has long been used in medical treatment of hypocalcemic and hyperkalemic states and should be administered in moribund patients who have the proper clinical history and clinical signs of hypocalcemia.

4. India pubmed.ncbi.nlm.nih.gov

The effect of calcium gluconate in the treatment of hyperkalemia. [2022] Intravenous (IV) calcium salts are routinely recommended as a cardio-protective therapy in the emergency treatment of severe hyperkalemia. However, this recommendation is supported by a low level of evidence and is anecdotal. The aim of this study is to determine the effectiveness of IV Calcium (Ca) gluconate in the treatment of hyperkalemia.

5. Switzerland pubmed.ncbi.nlm.nih.gov

The Use of Low-Calcium Hemodialysis in the Treatment of Hypercalcemic Crisis. [2019] We reviewed the results of low-calcium hemodialysis (LCHD; 1.25 mmol/L) in the treatment of 42 cases admitting with hypercalcemic crisis.

6. Ireland pubmed.ncbi.nlm.nih.gov

The amount of calcium in calcium chloride - Is there a need to clarify emergency treatment of hyperkalaemia algorithm? [2023] European Resuscitation Council (ERC) and American Heart Association (AHA) guidelines emphasize a rapid administration of calcium chloride (10 ml 10 % CaCl2) to protect the myocardium in the hyperkalaemia algorithm. However, calcium chloride preparations available in European markets vary from country to country. In our opinion, the drug dose recommended in the guidelines should not raise questions about the volume and amount of calcium in the intravenous supply and should be unambiguous to minimize the risk of error. Calcium dose should be given in terms of mmol/L or mEq or mg of calcium ions.

7. Ireland pubmed.ncbi.nlm.nih.gov

Effect of calcium in patients with pulseless electrical activity and electrocardiographic characteristics potentially associated with hyperkalemia and ischemia-sub-study of the Calcium for Out-of-hospital Cardiac Arrest (COCA) trial. [2023] The Calcium for Out-of-hospital Cardiac Arrest (COCA) trial was recently conducted and published. This pre-planned sub-study evaluated the effect of calcium in patients with pulseless electrical activity (PEA) including subgroup analyses based on electrocardiographic characteristics potentially associated with hyperkalemia and ischemia.

8. United States pubmed.ncbi.nlm.nih.gov

Verapamil reverses calcium cardiotoxicity. [2019] High circulating concentrations of calcium are toxic to the heart and may cause cardiac arrhythmias and arrest. To investigate the therapeutic use of calcium antagonists in hypercalcemia, we evaluated the efficacy of verapamil hydrochloride and magnesium chloride in the treatment of experimental calcium-induced cardiac arrest in laboratory rats. Verapamil rapidly reversed the experimental calcium-induced arrest and improved survival (83% survival versus 0% in controls). Magnesium failed to reverse this toxic event. We conclude from these experimental studies that verapamil may be useful in the treatment of hypercalcemic cardiac toxicity.

9. United States pubmed.ncbi.nlm.nih.gov

An intracellular-like cardioplegic solution. Its enhancement of myocardial protection. [2019] We sought to determine the relative protective effects of an intracellular-like, calcium-bearing, crystalloid solution (ICS) and a calcium-free, extracellular-like solution (ECS). Both solutions were similar in concentrations of potassium ions (25 to 26 mEq/L), in pH (7.7 to 7.8), and in osmolarity (340 to 360 mOsm/L). Normothermia was used to obviate masking the true effects of the solutions with the independent effects of hypothermia. Fifty-seven dogs were placed on cardiopulmonary bypass and had global myocardial ischemia for one hour. Continuous infusions and bolus injections into the aortic root of control solutions (n = 24), ECS (n = 15), and ICS (n = 16) were used. Two-hour postischemic ventricular performance was superior for ICS in comparison with ECS or control solutions regardless of administration mode. The multidose mode gave improved results with control and ECS groups. The use of an ICS yields improved postischemic performance in normothermic dog hearts.