In Vitro Fertilisation (IVF) Treatment Clinical Trial
Official title:
A Randomised, Double-blind, Parallel Groups, Placebo-controlled, Multi-centre Study Assessing the Effects of a Selective Oxytocin Antagonist (Barusiban) and a Mixed Oxytocin Antagonist - Vasopressin V1a Antagonist (Atosiban) Administered Intravenously on Luteal Phase Uterine Contractions in Oocyte Donors Supplemented With Vaginal Progesterone
The main purpose of this clinical research trial was to evaluate the effects of barusiban and atosiban compared to placebo on luteal phase uterine contractions in oocyte donors supplemented with progesterone.
This was a randomised, double-blind, parallel groups, placebo-controlled, multi-centre
trial. It was designed to evaluate the effects of a selective oxytocin antagonist
(barusiban) and a mixed oxytocin antagonist - vasopressin V1a antagonist (atosiban) on
uterine contractions during the luteal phase. Participants in this trial were oocyte donors
who had undergone controlled ovarian hyperstimulation in the long gonadotrophin-releasing
hormone (GnRH) agonist protocol or the multiple-dose or single-dose GnRH antagonist
protocols, received hCG for triggering of final follicular maturation and undergone oocyte
retrieval (OR). The duration of the trial was five days and participants attended the clinic
on three occasions: Day OR +1 (screening), Day OR +2 (randomisation and dosing of
investigational medicinal product), and Day OR +5 (end-of-trial).
After screening on Day OR +1, participants initiated luteal support supplementation with
vaginal progesterone, which continued throughout the trial. On Day OR +2, participants were
randomised to either barusiban, atosiban or placebo and participants received an intravenous
(IV) bolus followed by an IV infusion of either barusiban, atosiban or placebo for
approximately 4h. A mock embryo transfer was performed 3h after start of dosing.
Uterine contractility parameters were assessed by transvaginal ultrasound. The transvaginal
ultrasound recordings were analysed for uterine contractions by a central independent
assessor, blinded to treatment allocation
Definitions:
The frequency of uterine contractions was defined as the number of uterine contractions per
minute. A contraction was defined as one sequential upward and downward vertical
displacement of the endometrial / myometrial interface over time.
The external contractile measure was the mean wave amplitude in mm at the lumenal surface.
This metric was measured at the lumenal peaks and troughs only and was a measurement
designed to study the relationship between endometrial wave activity, manifested as bulk
motion of the uterus, versus internal contractile strength. The external contractile measure
was reported in mm/contraction.The external contractile measure quantified the movement of
the uterus as a whole as measured at the lumen, i.e. the motion of the uterus relative to
the body.
The internal contractile measure was the strength of the contractions based upon the sum of
the contraction amplitudes measured at the anterior and posterior endometrial / myometrial
interfaces. The amplitude at each interface was defined as the average difference between
the endometrial / myometrial-lumenal distance measured at the peaks and troughs of the
endometrial / myometrial interfaces. The internal contractile measure was reported in
mm/contraction. The internal contractile measure quantified the movement of the endometrium
relative to the lumen, i.e. the motion internal to the uterus.
The total contractile measure was the sum of the external contractile measure and the
internal contractile measure and quantified total muscle movement in the uterus. If the
waves at the anterior and posterior endometrial / myometrial interfaces were in phase then
there was no endometrial motion relative to the lumen and the motion was a pure wave motion
with the internal contractile measure equal to zero. The total contractile measure was
reported in mm/contraction.
Inter-subendometrial space was measured as the distance between the anterior stratum basalis
and posterior stratum basalis layers in mid-sagittal plane at an anatomic location between 5
and 10 mm from the fundus. All inter-subendometrial space measurements were made by
selecting a clear image of the uterus, waiting for any contractions to pass and freezing the
image.
A linear distance measurement was then taken between the anatomic landmarks described above.
Inter-subendometrial space was calculated from existing measurements using the mean of all
measurements identifying the endometrial-myometrial interfaces on the superior and inferior
surfaces in each endometrial strip when the arrows identifying endometrial contractions were
placed for motion analysis. Inter-subendometrial space was reported in mm
;
| Status | Clinical Trial | Phase | |
|---|---|---|---|
| Completed |
NCT01043120 -
Effect of Oxytocin Antagonist on Reduction of Uterine Contractions
|
Phase 2 |