Comparative Study Between Calcium Gluconate With Diosmin, Cabergoline and Cabergoline With Diosmin

• ClinicalTrials.gov Identifier: NCT06333691
• Recruitment Status: Completed
• First Posted: March 27, 2024
• Last Update Posted: March 27, 2024
• Sponsor: Minia University
• Information provided by (Responsible Party): Aya Mohammed Abdallah, Minia University

Tracking Information

• First Submitted Date: March 20, 2024
• First Posted Date: March 27, 2024
• Last Update Posted Date: March 27, 2024
• Actual Study Start Date: October 1, 2022
• Actual Primary Completion Date: February 1, 2024 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: March 20, 2024)

the incidence rate of moderate to severe OHSS. [ Time Frame: 3 months ]

OHSS is mainly characterized by abdominal distension, nausea, vomiting, diarrhea, hydrothorax, blood clotting disorders, and abnormal kidney function. Secondary outcomes included the clinical pregnancy rate, miscarriage rate, and live birth rate.

• Original Primary Outcome Measures: Same as current
• Change History: No Changes Posted
• Current Secondary Outcome Measures: Not Provided
• Original Secondary Outcome Measures: Not Provided
• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: Comparative Study Between Calcium Gluconate With Diosmin, Cabergoline and Cabergoline With Diosmin
• Official Title: Comparative Study Between Calcium Gluconate With Diosmin, Cabergoline and Cabergoline With Diosmin in Prevention of Ovarian Hyperstimulation Syndrome in High-risk Women Undergoing Intracytoplasmic Sperm Injection (ICSI) Procedures

Brief Summary

Ovarian hyperstimulation syndrome is a potentially fatal iatrogenic condition. This syndrome is characterized by a sudden increase of the vascular permeability which results in the development of a massive extravascular exudate in the peritoneal cavity, pleural, pericardium causing ascites, pleural and pericardial effusion.

Severe forms are also accompanied by electrolyte disturbances and cardiopulmonary, hepatic, renal, and hemoconcentration associated with increased thromboembolic risk.

This syndrome is avoidable by the judicious use of gonadotropins and careful monitoring of stimulation regimens.

Detailed Description

Ovarian hyperstimulation syndrome is a potentially fatal iatrogenic condition.

The major step to prevent hyperstimulation syndrome is to determine high risk patients as presence of polycystic ovarian syndrome, younger women with greater ovarian responsiveness, use of super active GnRH agonists, development of multiple immature and intermediate follicle during treatment, exposure to LH/hCG and previous history of hyperstimulation syndrome.

In addition, many different preventive modalities have been attempted such as decreasing the dose of FSH, using minimal or mild stimulating protocol as GnRH antagonists, use of insulin sensitizing agent as metformin, reduction the use of all follicles, decreasing the dose of hCG and administration of drugs which decrease capillary permeability as cabergoline, calcium gluconate, albumin, letrozole, hydroxyethyl starch and glucocorticoids.

Several different drugs have been used for prevention of hyperstimulation syndromes.

These include albumin, hydroxyethyl starch, aspirin, calcium, cabergoline, letrozole, and glucocorticoids. However, there is insufficient evidence about the benefits of these drugs in preventing hyperstimulation syndrome. Dopamine agonists (cabergoline) and calcium gluconate infusion are the most widely used preventive drugs.

Although these drugs have comparable effectiveness in preventing hyperstimulation syndrome with fewer maternal side effects, calcium maybe associated with arrhythmia

Recently attention has been focused on the use of Diosmin as a potent venotonic agent that decrease vascular permeability by reducing the release of inflammatory mediator such as prostaglandin E2 and thromboxane.

A study found that the combined use of diosmin and cabergoline in high-risk women undergoing ART was competent in avoiding hyperstimulation syndrome than using cabergoline alone. Moreover, this combination does not affect pregnancy rate, miscarriage nor multiple pregnancy

• Study Type: Interventional
• Study Phase: Not Applicable
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Prevention
• Condition: Ovarian Hyperstimulation Syndrome

Intervention

Drug: Calcium Gluconate

to compare the effectiveness of calcium gluconate, cabergoline and diosmin in preventing ovarian hyperstimulation syndrome in high-risk patient undergoing ICSI procedure.

Other Names:

• Cabergoline
• Diosmin

Study Arms

• Active Comparator: Group A:(Calcium gluconate Group)
  About 60 women patients,in which took IV infusion of calcium gluconate (Calcionate 10ml of 10% calcium gluconate, Memphis) in 200ml saline within 30 minutes of ovum pickup and contained for the next 3 days in addition to diosmin 2 tablets (500mg) t.d.s for 2 weeks.
  Intervention: Drug: Calcium Gluconate
• Active Comparator: Group B:(Cabergoline Group)
  About 60 women patients,in which took cabergoline (Dostinex 0.5 mg, Pfizer, Montreal, Canada) orally daily for 8 days after hCG triggering.
  Intervention: Drug: Calcium Gluconate
• Active Comparator: Group C:(Diosmin Group)
  About 60 women patients,in which took diosmin , 2 tablets (500mg) t.d.s for 2 weeks in addition to cabergoline 1 tablet 0.5 mg/day orally for 8 days starting at the day of hCG injection.
  Intervention: Drug: Calcium Gluconate

• Publications *: Not Provided

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: March 20, 2024): 180
• Original Actual Enrollment: Same as current
• Actual Study Completion Date: February 15, 2024
• Actual Primary Completion Date: February 1, 2024 (Final data collection date for primary outcome measure)

Eligibility Criteria

Inclusion Criteria:

• High risk patient for OHSS is defined as previous history of OHSS or > 24 antral follicles of the ovaries on base line ultrasound (polycystic ovary)
• During ovarian stimulation-increased number of small follicles (8-12 mm)
• High AMH
• Rapidly rising serum E2
• High serum E2 at hCG trigger (>3000 pg/ ml) or presence of > 20 follicles on the day of retrieval, by ultrasound examination or >20 oocytes retrieved

Exclusion Criteria:

• patients with endocrine disorder e.g diabetes mellitus, Cushing's disease, and congenital adrenal hyperplasia,
• Patients with hypertension,
• Patients systemic disease e.g asthma, collagen vascular disease, hypercholesterolemia and sickle cell anemia.

Sex/Gender

• Sexes Eligible for Study: Female

• Ages: 23 Years to 39 Years (Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Egypt

Administrative Information

• NCT Number: NCT06333691
• Other Study ID Numbers: Aya Mohammed
• Has Data Monitoring Committee: Yes

U.S. FDA-regulated Product

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

• IPD Sharing Statement: Not Provided
• Current Responsible Party: Aya Mohammed Abdallah, Minia University
• Original Responsible Party: Same as current
• Current Study Sponsor: Minia University
• Original Study Sponsor: Same as current
• Collaborators: Not Provided

Investigators

• Study Chair: Hatem Sarhan, Professor; Professor of Pharmaceutics, Faculty of Pharmacy, Minia University.

• PRS Account: Minia University
• Verification Date: March 2024