Pharmacokinetic Study on the Administration of Nadroparin Dosing Serum HGF in Gynecological Patients

Studio Pilota Farmacocinetico-clinico Sulla Somministrazione di Eparina a Basso Peso Molecolare e Dosaggio Sierico di HGF Nelle Pazienti Operate Affette da Patologie Ginecologiche

The purpose of this study is to determine whether HGF serum concentration might be raised in vivo by administering nadroparin given with prophylactic purpose to gynecological patients.

Study Overview

• Status: Completed
• Conditions: Urogenital Neoplasms; Ovarian Neoplasms; Genital Diseases, Female

Detailed Description

The study consisted of two phases. In the first phase, the main HGF pharmacokinetic parameters were evaluated, comparing a group of six women treated with a single dose of calcic nadroparin to a control group of six untreated women. Venous blood was drawn in both groups at 0, 30, 60, 90, 120, 150, 180, 240, 300, 360, 480 and 720 min. In the second phase, the HGF basal and maximum concentrations were measured in 17 women, undergoing one month of calcic nadroparin daily treatment. Venous blood was drawn twice on day 1 (at 0 and 90 min after nadroparin administration), then once on days 8 and 28 (at 90 min after LMWH injection). Calcic nadroparin was given subcutaneously at 2850 IU/0.3 ml anti-Xa.

Patients' characteristics:

In the first phase, 12 patients were enrolled, 6 treated with nadroparin for prophylactic anticoagulation and another 6 untreated as the control group. The six nadroparin-group patients were affected by benign pelvic gynaecologic diseases: three requiring laparoscopy and three laparotomy.

In the control group, four were healthy women volunteers and two patients submitted to gynaecological pelvic surgery, but these women were not treated with prophylactic LMWH.

In the second phase, 17 patients were enrolled among women planning gynaecological pelvic surgery and treated for 4 weeks with nadroparin for prophylactic anticoagulation. All these patients underwent laparotomy; ten were affected by malignancy (ECOC) and seven by benign (uterine fibroma, ovarian cystadenoma) pelvic gynaecologic diseases.

• Study Type: Observational
• Enrollment (Actual): 29

Contacts and Locations

Study Locations

• Italy
  • Turin, Italy
    • ASO Ordine Mauriziano

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Female

• Sampling Method: Non-Probability Sample

Study Population

primary care clinic gynecological patients (benign diseases, oncological diseases)

Description

Inclusion Criteria:

• ≥ 18 years
• ECOG PS ≤ 1
• Neutrophils ≥ 1500 l -1, platelets ≥ 150,000 l -1, creatinine 0.6 to 1.2 mg dl -1, total bilirubin ≤ 1 mg dL -1, AST ≤ 35 U l-1, ALT ≤ 45 U l-1

For patients in the study group: high-moderate risk of deep vein thrombosis (for the administration of LMWH for 30 days after surgery) under general anesthesia> 30 minutes, laparoscopy + at least one risk factor (age> 40 years, obesity, varicose veins, previous episode of deep vein thrombosis and / or pulmonary thromboembolism, thrombophilia, malignancy, prolonged immobility, congestive heart failure)

Exclusion Criteria:

• severe liver and renal disease
• diabetes
• hyperlipidemia
• marked osteoporosis
• HIV infection
• ongoing treatment with: immunosuppressive therapies, contraceptives, lipid-lowering drugs, NSAIDs, antiplatelet drugs, recent acute inflammatory or infectious (<3 weeks)
• a history of allergies,
• drug possible confounding, caffeine, tobacco, ethanol (must not have been hired in the last 24 hours prior to sampling)
• high risk of bleeding: peptic ulcer, history of hemorrhagic stroke, or bleeding disorders, severe hypertension, cerebral aneurysms, arteriovenous malformations, brain metastases

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

2

Cohorts and Interventions

Group / Cohort
Nadroparin/control (phase 1); patients affected by benign pelvic gynaecologic diseases were enrolled and treated with nadroparin for prophylactic anticoagulation; patients untreated with nadroparin were as control group.
Nadroparin (phase 2); patients were enrolled among women planning gynaecological pelvic surgery and treated for 4 weeks with nadroparin for prophylactic anticoagulation. All these patients underwent laparotomy;

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
AUC	HGF serum concentration	1 hour after nadroparin administration

Collaborators and Investigators

• Sponsor: Azienda Ospedaliera San Giovanni Battista
• Collaborators: University of Turin, Italy
• Investigators: Principal Investigator: Paolo Zola, MD, University of Turin, Italy

Publications and helpful links

General Publications

• Surbone A, Fuso L, Passera R, Ferrero A, Marchese C, Martino C, Luchin A, Di Renzo MF, Zola P. Daily administration of low molecular weight heparin increases Hepatocyte Growth Factor serum levels in gynaecological patients: pharmacokinetic parameters and clinical implications. BMC Res Notes. 2012 Sep 23;5:517. doi: 10.1186/1756-0500-5-517.

Study record dates

Study Major Dates

• Study Start: November 1, 2007
• Study Completion (Actual): November 1, 2008

Study Registration Dates

• First Submitted: July 5, 2011
• First Submitted That Met QC Criteria: January 30, 2012
• First Posted (Estimate): February 1, 2012

Study Record Updates

• Last Update Posted (Estimate): February 1, 2012
• Last Update Submitted That Met QC Criteria: January 30, 2012
• Last Verified: January 1, 2012

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Neoplasms by Site; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Neoplasms; Ovarian Neoplasms; Urogenital Neoplasms
• Other Study ID Numbers: FRFUnito60_07