Malignant Ascites in Ovarian Cancer: Impact of Total Paracentesis on Hemodynamics (ATLANTIS)

The ATLANTIS-study was designed to determine the safety of a full paracentesis in patients with malignant ascites due to ovarian cancer. The underlying hypothesis states, that full paracentesis does not impair safety, compared to fractioned paracentesis with clamping of the drain. Half of the patients will receive a full paracentesis, while the other half will receive fractioned paracentesis with clamping of the drain after 3 liters of ascites was evacuated. All patients receive extensive monitoring of hemodynamics and kidney function.

Study Overview

• Status: Completed
• Conditions: Ovarian Cancer; Hemodynamic Instability; Malignant Ascites
• Intervention / Treatment: Procedure: Paracentesis

Detailed Description

Background: Malignant ascites is common in ovarian cancer and often causes symptoms such as abdominal pressure and shortness of breath, resulting in an decreased quality of life for the patient. Paracentesis is a safe and easy method for symptom relief. But no guidelines exist on the management of ascites drainage in ovarian cancer. In many cases a partial paracentesis is performed, due to fear of hemodynamic instability or kidney failure, with partial drainage of the intraperitoneal fluid on the first day and subsequent drainage on the next day. As there is no study that reported a deteriorated health due to full paracentesis in ovarian cancer, the decision whether a partial or total paracentesis is performed depends entirely on the department or the physician.

Since a total paracentesis can be performed as an out-patient treatment, this approach is often preferred by the patient. Full paracentesis is also more efficient and cost-effective.

The objective of the ATLANTIS-study is to prove the safety of total paracentesis regarding hemodynamic changes and kidney failure.

Methods: ATLANTIS is a randomized, prospective, clinical study that aims to include 60 patients. Patients with histologically confirmed epithelial ovarian, fallopian tube and peritoneal cancer are randomized into two arms: Partial (3 Liter) and total paracentesis. Before, during and for two hours after the paracentesis, an advanced hemodynamic monitoring is performed to ensure the patients' safety. The monitoring includes mean arterial pressure and stroke volume. After the initial phase of extensive monitoring (2 hours), the blood pressure is measured for a period of 24 hours to evaluate not only short term, but also long-term hemodynamic changes. Before and 24 hours after the paracentesis, blood samples are analyzed to detect a potential acute kidney failure.

• Study Type: Interventional
• Enrollment (Actual): 61
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Germany
  • Berlin, Germany, 13353
    • Charite-University Medicine of Berlin, Department of Gynecology-Campus Virchow Klinikum

Participation Criteria

Eligibility Criteria

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

Description

Inclusion criteria:

• Histologically confirmed ovarian cancer, peritoneal cancer or fallopian tube cancer
• Symptomatic (e.g. abdominal pressure, pain, shortness of breath) malignant ascites with clinical indication for paracentesis and sonographic estimate of >3 liters
• Patient information and written informed consent

Exclusion criteria:

• Age <18 years
• Missing written informed consent
• Lack of sufficient knowledge of german or english language
• No willingness to consent to the storage or distribution of anonymised disease-specific data inside the clinical trial
• Placement inside a state facility due to judicial order
• Employee status at Charite-University Medicine of Berlin
• Chronic kidney insufficiency defined as serum creatinin levels >1,2 g/dl at time point of admission
• Active neurologic/psychiatric disorder at time point of admission
• Cardiac insufficiency defined as >NYHA I at time point of admission
• Manifest ileus at time point of admission
• Manifest chronic arterial hypo- or hypertension, defined as chronic baseline systolic pressure of <90 or >140 mmHg and diastolic pressure of <70 and >90 mmHg
• Active infection
• Blood clotting disorder (congenital or acquired)
• Thrombocytopenia (platelets <80 000/nl)
• Active participation in another clinical intervention trial at time point of admission
• Chronic atrial fibrillation on time point of admission
• Status post cardiac pacer implantation
• Liver cirrhosis
• Liver metastases

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Supportive Care
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Other: Full paracentesis; All ascites is drained	Procedure: Paracentesis; Full versus partial paracentesis (3 liters)
Other: Fractioned paracentesis; 3 Liters are drained, then the drain is clamped and the rest of the ascites is drained on the next day	Procedure: Paracentesis; Full versus partial paracentesis (3 liters)

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Change of stroke volume	Stroke volume is measured by advanced hemodynamic monitoring	20 minutes prior to paracentesis, during paracentesis up to the end of paracentesis, an average of 50 minutes
Change of mean arterial pressure	Mean arterial pressure is measured by advanced hemodynamic monitoring	20 minutes prior to paracentesis, during paracentesis up to the end of paracentesis, an average of 50 minutes

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Incidence of side effects in the post-paracentesis interval	Incidence of hypotension (medical intervention indicated) and impairment of kidney function (KIDIGO criteria)	24 hours after the finish of the paracentesis
Incidence of symptoms in the post-paracentesis interval	Incidence of hypotension (medical intervention indicated) and impairment of kidney function (KIDIGO criteria)	24 hours after the finish of the paracentesis
Change of stroke volume in the post-paracentesis interval	Stroke volume is measured by advanced hemodynamic monitoring	2 hours after the finish of the paracentesis
Change of mean arterial pressure in the post-paracentesis interval	Mean arterial pressure is measured by advanced hemodynamic monitoring	2 hours after the finish of the paracentesis
Change of laboratory values	Measurement in plasma (Blood count, creatinin, AST, ALT, urea, aldosterone, renin, sodium, potassium, albumin, C-reactive protein, leukocytes)	Serial measurements: 2 hours prior to paracentesis, 24 hours after paracentesis
Urine excretion	Urin volume	24 hours after the finish of paracentesis
Quality of life- pre and post paracentesis: EQ-5D questionnaire	Measured with the EuroQuol-Group 5 Dimensions - Visual analog scale (EQ-5D VAS) questionnaire, the questionnaire directs to characterize the quality of life by mobility, activities, pain and fear and subjective scale between 1 (worst) and 100 (best)	2 hours before paracentesis, 24 hours after paracentesis and 1 week after paracentesis
Ascites related symptoms- pre and post paracentesis	Measured with the and Functional Assessment of Chronic Illness Therapy-Ascites Index (FACIT-AI) questionnaire, the questionnaire directs to characterise the symptoms associated to ascites regarding 13 factors e.g. appetite, sleep, activities, symptoms, emotional distress by 0 to 4 points. The maximum score is 52 (best result: 13x4), 0 is the minimum score (worst result 13x0)	2 hs before paracentesis, 24-hours after paracentesis and 1 week after paracentesis
Measurement of exact drainage volume	Measurement of exact drainage volume in millilitre	Within 1 hour after the finish of paracentesis
VEGF (vascular endothelial growth factor) level	Measurement of the concentration of hormone vascular endothelial growth factor in ascites	Within 1 hour after the finish of paracentesis
Change of venous return and mean systemic filling pressure	Venous return and mean systemic filling pressure is measured by advanced hemodynamic monitoring	20 minutes prior to paracentesis, during paracentesis up to the end of paracentesis, an average of 50 minutes

Collaborators and Investigators

• Sponsor: Charite University, Berlin, Germany
• Investigators: Principal Investigator: Klaus Pietzner, MD, Charite-University Medicine of Berlin, Department of Gynecology

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2017
• Primary Completion (Actual): August 9, 2019
• Study Completion (Actual): September 9, 2019

Study Registration Dates

• First Submitted: February 11, 2018
• First Submitted That Met QC Criteria: July 23, 2019
• First Posted (Actual): July 25, 2019

Study Record Updates

• Last Update Posted (Actual): December 8, 2020
• Last Update Submitted That Met QC Criteria: December 6, 2020
• Last Verified: July 1, 2019

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Pathologic Processes; Neoplasms by Histologic Type; Neoplasms; Urogenital Neoplasms; Neoplasms by Site; Carcinoma; Neoplasms, Glandular and Epithelial; Genital Neoplasms, Female; Endocrine System Diseases; Ovarian Diseases; Adnexal Diseases; Gonadal Disorders; Endocrine Gland Neoplasms; Ovarian Neoplasms; Ascites; Carcinoma, Ovarian Epithelial
• Other Study ID Numbers: EA 1/224/16

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: Undecided

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No