The Effect of Carbetocin on Cardiac Repolarization: A Randomized, Placebo- and Positive-Controlled QT/QTc Study in Healthy Adults
In brief
Carbetocin's estimated QTc increase was 4.5 milliseconds at high exposure
In 42 healthy adults, a single intravenous carbetocin infusion produced an estimated placebo-corrected QTc increase of 4.5 milliseconds at high clinical exposure, below the 10-millisecond threshold of concern. Because carbetocin also raised heart rate, researchers used an individualized correction method; the results are reassuring for a single dose, but do not establish effects with repeated use or in postpartum patients.
- Journal
- Clinical and translational science (Q1)
- Published
- 1 October 2026
- Study design
- Randomized controlled trial
- Evidence level
- Level 1, High (CEBM 1b)
- Authors
- Daniël M Jonker, Katie Barletta, Ekaterine Bagci, Kyle Raymond, Philippe Pinton
- PMID
- 42802704
- DOI
- 10.1111/cts.70735
Why clinicians should know about it
- Picked for Pharmacology (medical) (paper of the day, 29 September 2026): Phase I QT study, cardiac safety assessment
Abstract
Carbetocin is an oxytocin receptor agonist used for postpartum hemorrhage prevention. While oxytocin is known to transiently prolong the QT/QTc interval, robust QTc data for carbetocin are limited. Carbetocin is known to elevate HR, which can impact QTc analyses; thus, a dose that did not overly elevate HR was important to select. This randomized, placebo- and positive-controlled trial evaluated the effect of a single intravenous infusion of a supratherapeutic dose (650 μg) of carbetocin over 45 min on cardiac repolarization in healthy adults (N = 42). Continuous cardiodynamic ECGs were recorded from 45 min before through 24 h after dosing. The primary endpoint was placebo-corrected change from baseline in QT interval (ΔΔQTc) using the most appropriate heart rate (HR) correction method. The primary analysis was based on exposure-response modeling of the relationship between carbetocin plasma concentrations and ΔΔQTc, to identify an effect ≥ 10 msec at the high clinical exposure. During intravenous infusion of carbetocin, the mean HR change from baseline reached a maximum of 16.7 bpm. Multiple correction methods for HR were assessed, and the placebo-corrected, optimized, individualized heart rate-corrected QT interval (oQTcI) was found to be adequate. The estimated mean placebo-corrected oQTcI change from baseline was 4.5 msec (90% CI: 3.4, 5.6) at the high clinical exposure level of 12.4 ng/mL following a single intravenous infusion of 867 μg/h carbetocin. Exposure-response models for carbetocin established no predicted QTc prolongations of clinical or regulatory concern (≥ 10 msec) at the high clinical exposure level. Trial Registration: ClinicalTrials.gov Registration: NCT05924321.
Abstract as published, via PubMed.
For healthcare professionals. The summary is generated by AI from the published abstract, and the evidence level is assigned automatically from the study design on the Oxford CEBM hierarchy. Neither is medical advice. Read the full paper before changing practice.