Effect of the Uterotonic Carbetocin on Acute Post Cesarean-Section Pain

Study Overview
=================
Brief Summary
-----------------
Carbetocin is an oxytocin agonist used for prevention of postpartum bleeding after cesarean delivery. First studies revealed in 2012 an analgesic effect of carbetocin, compared to its parent substance oxytocin. This study will enroll 78 women undergoing cesarean delivery. In a double-blind, prospective design patients will be either attributed to the oxytocin or the carbetocin study arm. The primary endpoint will be the area of hyperalgesia around the cesarean delivery scar. This will be performed with a von Frey hair, resulting in a unpleasant feeling in the area of hyperalgesia.

Official Title
-----------------
Effect of the Uterotonic Carbetocin on Acute Post Cesarean-Section Pain, A Prospective Randomised Study

Conditions
-----------------
Cesarean Delivery

Intervention / Treatment
-----------------
* Drug: Carbetocin


Participation Criteria
=================
Eligibility Criteria
-----------------
Inclusion Criteria: Age 18-45, uneventful pregnancy, on term (>37 0/7 weeks of gestation), scheduled elective CS including repeat CS Exclusion Criteria: lack of informed consent, active labor, multiple pregnancy, polyhydramnios, severe fetal malformations

Ages Eligible for Study
-----------------
Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
-----------------
Female

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| No Intervention: Oxytocin<br>Oxytocin 20 IE in 500 ml G Na intravenous infusion over 6 hours (GlucoSalin 2:1; 2/3 glucose 5%+1/3 NaCl 0.9%), Sintetica-Bioren, Switzerland, after birth of the baby. For blinding purposes a 3ml NaCl 0.9% syringe is administered intravenously after birth of the baby as well. | |
| Experimental: Carbetocin<br>100 mcg of Carbetocin, Ferring, Switzerland, as iv administration after birth of the baby. For blinding purposes an intravenous infusion of 500 ml G Na (GlucoSalin 2:1; 2/3 glucose 5%+1/3 NaCl 0.9%) is administered over 6 hours. | Drug: Carbetocin<br>* Postpartum uterotonic drug<br>* Other names: Pabal, Ferring, Baar, Switzerland;|

What is the study measuring?
-----------------
Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Cesarean delivery scar cutaneous hyperalgesia | In the area of the cesarean delivery scar, the area of dynamic secondary hyperalgesia for punctate mechanical stimuli around the surgical incision will be measured around her scar according to the method described by Stubhaug et al. In brief, stimulation with a Von Frey Filament (225.1gr) is started from outside the hyperalgesic area where no pain sensation is experienced toward the incision until the patient reports a distinct change in perception. The first point where a painful, sore, or sharp feeling appears is recorded, and the distance to the incision is measured. If no change in sensation appears, stimulation is stopped at 0.5 cm from the incision. The area of secondary hyperalgesia is determined by testing along radial lines separated by 5 cm around the incision. The observations are translated onto graph paper, and the surface is calculated as cm2/cm of incision. | 4 hours after cesarean delivery | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Pressure pain detection threshold | Pain detection thresholds will be measured with an electronic pressure algometer (Algometer, Somedic, Denmark) applied at the center of the pulp of the 2nd toe. The probe has a surface area of 1 cm2. The pressure is increased from 0 at a rate of 30kPa/s to a maximum pressure of 1000kPa. Pain detection threshold is defined as the point at which the pressure sensation turns to pain. The subjects are instructed to press a button when these points are reached. The algometer displays the pressure intensity at which the button is pressed. If the subjects do not press the button at a pressure of 1000 kPa, this value is considered as threshold. | before cesarean | 
| Pressure pain detection threshold | Pain detection thresholds will be measured with an electronic pressure algometer (Algometer, Somedic, Denmark) applied at the center of the pulp of the 2nd toe. The probe has a surface area of 1 cm2. The pressure is increased from 0 at a rate of 30kPa/s to a maximum pressure of 1000kPa. Pain detection threshold is defined as the point at which the pressure sensation turns to pain. The subjects are instructed to press a button when these points are reached. The algometer displays the pressure intensity at which the button is pressed. If the subjects do not press the button at a pressure of 1000 kPa, this value is considered as threshold. | 4 hours after cesarean | 
| Pressure pain detection threshold | Pain detection thresholds will be measured with an electronic pressure algometer (Algometer, Somedic, Denmark) applied at the center of the pulp of the 2nd toe. The probe has a surface area of 1 cm2. The pressure is increased from 0 at a rate of 30kPa/s to a maximum pressure of 1000kPa. Pain detection threshold is defined as the point at which the pressure sensation turns to pain. The subjects are instructed to press a button when these points are reached. The algometer displays the pressure intensity at which the button is pressed. If the subjects do not press the button at a pressure of 1000 kPa, this value is considered as threshold. | 24 hours after cesarean | 
| Pressure pain detection threshold | Pain detection thresholds will be measured with an electronic pressure algometer (Algometer, Somedic, Denmark) applied at the center of the pulp of the 2nd toe. The probe has a surface area of 1 cm2. The pressure is increased from 0 at a rate of 30kPa/s to a maximum pressure of 1000kPa. Pain detection threshold is defined as the point at which the pressure sensation turns to pain. The subjects are instructed to press a button when these points are reached. The algometer displays the pressure intensity at which the button is pressed. If the subjects do not press the button at a pressure of 1000 kPa, this value is considered as threshold. | 48 hours after cesarean | 
| Pressure pain detection threshold | Pain detection thresholds will be measured with an electronic pressure algometer (Algometer, Somedic, Denmark) applied at the center of the pulp of the 2nd toe. The probe has a surface area of 1 cm2. The pressure is increased from 0 at a rate of 30kPa/s to a maximum pressure of 1000kPa. Pain detection threshold is defined as the point at which the pressure sensation turns to pain. The subjects are instructed to press a button when these points are reached. The algometer displays the pressure intensity at which the button is pressed. If the subjects do not press the button at a pressure of 1000 kPa, this value is considered as threshold. | 6 weeks after cesarean | 
| Baseline depression detection | Beck Depression Inventory (BDI-II): a 21 question multiple choice inventory used to measure severity of depression. This will be used in order to assess an eventual prepartum depression, this measure aims at eliminating bias if detecting a postpartum depression by the Edinburgh Depression questionnaire | before cesarean | 
| Postpartum depression | Assessment of postpartum depression with the Edinburgh Postnatal Depression Scale. It is a 10 item questionnaire. | 6 weeks post cesarean | 
| Cesarean delivery scar cutaneous hyperalgesia | In the area of the cesarean delivery scar, the area of dynamic secondary hyperalgesia for punctate mechanical stimuli around the surgical incision will be measured around her scar according to the method described by Stubhaug et al. In brief, stimulation with a Von Frey Filament (225.1gr) is started from outside the hyperalgesic area where no pain sensation is experienced toward the incision until the patient reports a distinct change in perception. The first point where a painful, sore, or sharp feeling appears is recorded, and the distance to the incision is measured. If no change in sensation appears, stimulation is stopped at 0.5 cm from the incision. The area of secondary hyperalgesia is determined by testing along radial lines separated by 5 cm around the incision. The observations are translated onto graph paper, and the surface is calculated as cm2/cm of incision. | 24 hours after cesarean | 
| Cesarean delivery scar cutaneous hyperalgesia | In the area of the cesarean delivery scar, the area of dynamic secondary hyperalgesia for punctate mechanical stimuli around the surgical incision will be measured around her scar according to the method described by Stubhaug et al. In brief, stimulation with a Von Frey Filament (225.1gr) is started from outside the hyperalgesic area where no pain sensation is experienced toward the incision until the patient reports a distinct change in perception. The first point where a painful, sore, or sharp feeling appears is recorded, and the distance to the incision is measured. If no change in sensation appears, stimulation is stopped at 0.5 cm from the incision. The area of secondary hyperalgesia is determined by testing along radial lines separated by 5 cm around the incision. The observations are translated onto graph paper, and the surface is calculated as cm2/cm of incision. | 48 hours after cesarean | 
| Cesarean delivery scar cutaneous hyperalgesia | In the area of the cesarean delivery scar, the area of dynamic secondary hyperalgesia for punctate mechanical stimuli around the surgical incision will be measured around her scar according to the method described by Stubhaug et al. In brief, stimulation with a Von Frey Filament (225.1gr) is started from outside the hyperalgesic area where no pain sensation is experienced toward the incision until the patient reports a distinct change in perception. The first point where a painful, sore, or sharp feeling appears is recorded, and the distance to the incision is measured. If no change in sensation appears, stimulation is stopped at 0.5 cm from the incision. The area of secondary hyperalgesia is determined by testing along radial lines separated by 5 cm around the incision. The observations are translated onto graph paper, and the surface is calculated as cm2/cm of incision. | 6 weeks after cesarean |