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Cabergoline Reduces OHSS

Primary Purpose

Ovarian Hyperstimulation Syndrome

Status
Completed
Phase
Phase 3
Locations
Study Type
Interventional
Intervention
Cabergoline
MR
Ultrasound
Blood Analysis
Sponsored by
Instituto Valenciano de Infertilidad, IVI VALENCIA
About
Eligibility
Locations
Outcomes
Full info

About this trial

This is an interventional prevention trial for Ovarian Hyperstimulation Syndrome focused on measuring Ovarian hyperstimulation syndrome, dopamine agonists, cabergoline, hemoconcentration, ascites, ovarian perfusion, dopamine receptor 2

Eligibility Criteria

18 Years - 35 Years (Adult)FemaleAccepts Healthy Volunteers

Inclusion Criteria:

  • 18 - 35 years old healthy women, with risk of developing OHSS.

Exclusion Criteria:

  • No risk of developing OHSS; < 20 oocytes retrieved.

Sites / Locations

    Outcomes

    Primary Outcome Measures

    Secondary Outcome Measures

    Full Information

    First Posted
    February 23, 2007
    Last Updated
    February 26, 2007
    Sponsor
    Instituto Valenciano de Infertilidad, IVI VALENCIA
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    1. Study Identification

    Unique Protocol Identification Number
    NCT00440258
    Brief Title
    Cabergoline Reduces OHSS
    Official Title
    Dopamine Agonist Cabergoline Reduces Hemoconcentration and Ascites in Hyperstimulated Women Undergoing Assisted Reproduction.
    Study Type
    Interventional

    2. Study Status

    Record Verification Date
    February 2007
    Overall Recruitment Status
    Completed
    Study Start Date
    April 2004 (undefined)
    Primary Completion Date
    undefined (undefined)
    Study Completion Date
    July 2006 (undefined)

    3. Sponsor/Collaborators

    Name of the Sponsor
    Instituto Valenciano de Infertilidad, IVI VALENCIA

    4. Oversight

    Data Monitoring Committee
    No

    5. Study Description

    Brief Summary
    The present study was designed to provide clinical confirmation of Cb2's value as a new approach in the prevention of increased vascular permeability and hemoconcentration, both signs of OHSS in humans, and in order to explore its mechanism of action. To this end, a prospective, randomized, placebo-controlled study was designed in which Cb2 was employed in women at risk of OHSS after gonadotropin administration for ART. Simultaneously, ovarian perfusion was assessed in these patients using MR pharmacokinetic modeling.
    Detailed Description
    Patients and Study design This study was performed in 82 oocyte donors between April 2004 and July 2006. The study protocol was approved by our institution's Ethical Committee and all participants signed a written consent form. The protocol for COH has previously been described (23). Only patients at risk of developing OHSS were included. The definition of risk was the development of 20-30 follicles >12 mm in diameter, and retrieval of >20 oocytes. Once the decision to administer hCG was taken, patients were immediately allocated into two groups based on a computer randomization: the study group initially consisted of 41 patients, but 6 of these were discarded after randomization because <20 oocytes were retrieved despite the development of >20 follicles >12 mm. Thus, a remaining total of 35 patients received one 0.5 mg tablet of Cb2 daily for eight days. The control group was also initially composed of 41 women. However, 7 of these did not meet the criteria of number of oocytes retrieved, and 2 donors decided to withdraw themselves from the study. This left a remaining total of 32 women, all of whom completed the study, and who received a placebo tablet daily for 8 days. Women were monitored every 48 hours from the day of hCG (day 0) until day 8. On day hCG+4, in order to define ascites, and provided that there was a certain degree of fluid in the pouch of Douglas after ovum pick-up, we employed transvaginal ultrasound (TVU) to measure two major perpendicular diameters of fluid pockets in 15 donors who showed no risk of OHSS. We observed 3.5±2.8 cm2 of fluid in the pelvis in normal conditions. Therefore, the existence of ascites was confirmed when a pocket of peritoneal fluid >9 cm2 was observed when the patient was in lithotomy position (with the gynecological table always at 45º from the floor of the room), which is the result of the mean± 2 standard deviations (SD) of the value found in non-OHSS candidates. TVU scans were performed by the same researcher (CA), who was blind to the treatment to which the patient was submitted. A 6.5 MHz vaginal probe (Voluson 730 Pro V, General Electric, Madrid, Spain) was employed for all TVU scans. To evaluate the biochemical risk of hemoconcentration, we evaluated hemoglobin, hematocrit, and leukocyte count. Moreover, renal (creatinine) and liver [transaminases: aspartate aminotransferase (AST); alanine aminotransferase (ALT)] functions, and electrolytes (Na, K) were analyzed to ascertain the severity of the syndrome. Since all women undergoing ART experience a certain degree of discomfort and enlarged ovaries (known as mild OHSS), we centered our attention on analyzing the incidence of moderate and severe OHSS, which were identified according to our modified (24) classification of Golan et al (25). Moderate OHSS was confirmed when a patient presented ultrasonographic evidence of ascites, while diagnosis of severe OHSS required clinical evidence of ascites and/or hydrothorax and breathing difficulties, or one of the following criteria: a) increased blood viscosity due to hemoconcentration (hemoglobin ≥15 g/dl, hematocrit ≥45%, or leukocyte count ≥20,000/mm3); b) coagulation abnormality; c) diminished renal perfusion and function (serum creatinine levels >1.2 mg/dl); d)liver dysfunction: defined when transaminases (AST or ALT) were >40 U/ml (24, 25). Additionally, serum PRL levels were measured and adverse drug reactions recorded. An end-of-study assessment was scheduled 7-10 days after the last dose of Cb2/placebo. Moreover, in the first 8 patients included in the study, follicular fluid aspirates without obvious blood contamination were collected, pooled and and mRNA extracted to quantify the amount of Dp-r2 in human ovaries, employing two different molecular techniques. To further objectively analyze changes in vascular permeability and fluid shifts, confirmatory studies were performed on six women in the study group and four controls, employing magnetic resonance (MR) as described below. Dynamic contrast-enhanced MR was performed at three different stages of the study: at baseline, before gonadotropin administration was initiated; just before hCG injection; and on day hCG+5, after oocyte pick-up.

    6. Conditions and Keywords

    Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
    Ovarian Hyperstimulation Syndrome
    Keywords
    Ovarian hyperstimulation syndrome, dopamine agonists, cabergoline, hemoconcentration, ascites, ovarian perfusion, dopamine receptor 2

    7. Study Design

    Primary Purpose
    Prevention
    Study Phase
    Phase 3
    Interventional Study Model
    Parallel Assignment
    Masking
    Double
    Allocation
    Randomized
    Enrollment
    60 (false)

    8. Arms, Groups, and Interventions

    Intervention Type
    Drug
    Intervention Name(s)
    Cabergoline
    Intervention Type
    Procedure
    Intervention Name(s)
    MR
    Intervention Type
    Procedure
    Intervention Name(s)
    Ultrasound
    Intervention Type
    Procedure
    Intervention Name(s)
    Blood Analysis

    10. Eligibility

    Sex
    Female
    Minimum Age & Unit of Time
    18 Years
    Maximum Age & Unit of Time
    35 Years
    Accepts Healthy Volunteers
    Accepts Healthy Volunteers
    Eligibility Criteria
    Inclusion Criteria: 18 - 35 years old healthy women, with risk of developing OHSS. Exclusion Criteria: No risk of developing OHSS; < 20 oocytes retrieved.
    Overall Study Officials:
    First Name & Middle Initial & Last Name & Degree
    Antonio Pellicer, MD
    Organizational Affiliation
    IVI VALENCIA
    Official's Role
    Study Director

    12. IPD Sharing Statement

    Learn more about this trial

    Cabergoline Reduces OHSS

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