Comparing the Dose-response Profiles of Uterotonics After Initial Carbetocin Administration - an Ex-vivo Study in Desensitized Human Myometrium

Trial statusRecruiting
Trial phaseNot applicable
Trial typeInterventional
Biological sexFemale
Age18-45
SponsorSamuel Lunenfeld Research Institute, Mount Sinai Hospital

About this trial

This study will investigate the effects of drugs called "uterotonics" that help with the contraction of the uterus after a baby is born. This uterine contraction is very important to stop the bleeding after delivery. An uncontracted uterine state is called "uterine atony", which can lead to an excessive amount of post-delivery bleeding. Carbetocin is an uterotonic drug that works well to prevent post-delivery bleeding. In some cases, carbetocin is not enough to contract the uterus, and ongoing bleeding continues. When that happens, there are other uterotonic medications that can be used. In this study, we aim to find which uterotonic drug, amongst those available (oxytocin, carbetocin, ergometrine or carboprost), is more effective to lower the risk of post-delivery bleeding once carbetocin has already been administered.

This study will be done by using a very small sample of uterine tissue, taken from the incision site, following delivery by cesarean section. The sample is taken to the laboratory and will be exposed to carbetocin followed by other uterotonic drugs. The information obtained from this study will help modify the treatment for uterine atony and post-delivery bleeding to lower the risk further.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

Patients who give written consent to participate in this study

Patients with gestational age 37-41 weeks

Non-laboring patients, not exposed to exogenous oxytocin

Patients requiring elective primary or first repeat CD

Disqualifiers

Patient refusal

Patients who require general anesthesia

Patients in labour and those receiving oxytocin for induction of labour

Emergency CD

Trial design

Design model

Parallel

Treatments tested in this trial

  • Carbetocin

    Drug

    Carbetocin first bolus 10-8 M (equivalent to 100 mcg) will be added to the muscle bath to create ex-vivo environment similar to Cesarean delivery, and after 20 minutes the baths will be washed three time with physiological salt solution (PSS).

  • Oxytocin

    Drug

    Oxytocin 10-5M will be added to all strips for 2 hours to induce desensitization.

  • Carbetocin

    Drug

    Increasing concentrations of carbetocin in a pattern of 1 log molar increase every 10 min, from 10-5 M to 10-5 M

  • Oxytocin

    Drug

    Increasing concentrations of oxytocin from 10-10 M to 10-5 M

  • Ergonovine

    Drug

    Increasing concentrations of ergometrine from 10-10 M to 10-5 M

  • Carboprost

    Drug

    Increasing concentrations of carboprost from 10-10 M to 10-5 M

Treatment groups

32 Participants
are divided into 5 treatment groups
Group A: CarbetocinActive comparator 2 interventions
Group B: OxytocinActive comparator 2 interventions
Group C: ErgometrineActive comparator 3 interventions
Group D: CarboprostActive comparator 3 interventions
Group E: ControlPlacebo comparator 2 interventions

Trial outcomes

Primary outcomes

1

Motility index

Motility index (MI) is a calculated outcome, based on the formula: frequency/(10 x amplitude). Frequency and amplitude are secondary outcome measures as described below. The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.

Time frame
4 hours

Secondary outcomes

1

Amplitude of contraction

The maximum extent of uterine muscle contraction, measured in grams (g). The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.

Time frame
4 hours
2

Frequency of contraction

The number of contractions in uterine muscle (myometrium) over 10 minutes, spontaneously and in response to an agonist. The analysis is undertaken by attaching myometrial strips between an isometric force transducer and the base of an organ bath chamber.

Time frame
4 hours
3

Integrated area under response curve (AUC)

Time frame
4 hours

Other outcomes

Sponsors and contacts

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