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

Study Overview
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Brief Summary
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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.

Detailed Description
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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.

Official Title
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Malignant Ascites in Ovarian Cancer: Impact of Total Paracentesis on Hemodynamics

Conditions
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Malignant Ascites, Ovarian Cancer, Hemodynamic Instability

Intervention / Treatment
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* Procedure: Paracentesis


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

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


Arms and Interventions

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

What is the study measuring?
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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 |