Glucagon's Cardiovascular Effects With and Without Beta-blocker-induced Cardioinhibition

What Was Tested

The trial (phase 4) is built around Glucagon.

This trial investigates effects of a glucagon bolus injection on heart rate, blood pressure and cardiac output during beta-blocker-induced cardiodepression.

It had five arms (groups): Esmolol-placebo+glucagon 1 placebo (A) (experimental), Esmolol+glucagon 1 placebo (B) (experimental), Esmolol+glucagon 1 (C) (experimental), Esmolol-placebo+glucagon 2 (D) (experimental) and Esmolol-placebo+glucagon 1 (E) (experimental).

The registry classes the interventions as drug.

More on the Plan

It is important to keep in mind that the knowledge about glucagon's effects in poisoning situations is derived from uncontrolled cohort studies and case reports as well as animal studies \[3,8\].

Therefore, the overall level of evidence pertaining to glucagon in the management of beta-blocker overdoses is low.

The purpose of this participant- and outcome assessor blinded, randomized placebo-controlled crossover clinical trial is to investigate the effects of intravenous glucagon on the circulation alone or during beta-blocker-induced heart (rate) suppression.

The trial includes a total of six visits; a screening visit and five trial days as described under Arms and Interventions.

Who Took Part

10 actual participants took part.

It was open to men only aged from 18 years up to 40 years.

Healthy volunteers could join, not only people with the condition.

Examples of who could join: Healthy male determined by investigator, based upon physical examination, medical history, ECG, vital signs and laboratory results. Body mass index (BMI) ≥ 18.5 and ≤ 29.9 kg/m2 and body weight between 50 and 100 kg, inclusive, at screening visit.

The full record lists 2 inclusion and 14 exclusion criteria; among the exclusions: abnormal blood levels of sodium, potassium, creatinine, alanine transaminase (alt), alkaline phosphatase, albumin, bilirubin, hemoglobin, hba1c, cholesterol fractions; bradycardia (\<45 beats per minute); hypotension (systolic blood pressure \< 100 mmhg).

How the Study Was Run

It was run as a randomized, crossover and double-blind study.

Because people in this Glucagon study were split into groups at random, differences between the groups are less likely to reflect who happened to join each one.

Each person switched between Glucagon and the comparison at some point, usually with a gap in between.

Blinding on both sides kept the participants and researchers unaware of who received Glucagon.

Those kept unaware of assignments: participant and outcomes assessor.

It started in 2018-06-01 with completion listed for 2019-10-01.

It ran at 1 site in Denmark.

Its stated primary purpose is basic science.

What Was Measured

Primary outcome: Heart rates on the esmolol+glucagon-day compared to the esmolol+placebo-day (2 minute average) (time frame: Glucagon bolus + 5±1 minute).

It also tracked 6 secondary outcomes, for example Change in heart rate from baseline compared between study days, Change in stroke volume (ml) from baseline compared between study days, Change in systolic, diastolic and mean arterial pressure (mmHg) from baseline compared between study days, Effects of glucagon on blood glucose compared to placebo and Adverse effects of glucagon.

What This Means in Plain Language

Put simply, this is a phase 4, randomized trial of Glucagon in 10 people.

Its size is small, so on its own it can only give an early look.

The trial is marked completed; no results are posted to the registry yet, so nothing here describes outcomes.

More context: the Glucagon compound page, all human trials.