Efficacy of Combining Pasireotide With Aspiration Sclerotherapy to Improve Volume Reduction of Hepatic Cysts

Phase 3

Completed

• Conditions: Symptomatic Dominant Liver Cyst
• Interventions: Drug: Pasireotide LAR 60 mg; Procedure: Aspiration sclerotherapy; Drug: Placebo

• Registration Number: NCT02048319
• Lead Sponsor: Radboud University Medical Center

Brief Summary

Liver cysts are fluid filled cavities located in the liver. They are present in 2-11% of the general population, typically not causing any symptoms or complications. However, in a small subset of patients complaints of pain, abdominal fullness and distension, dyspnea and nausea occur.

Currently, aspiration and sclerotherapy is a treatment of choice in symptomatic patients with a large dominant liver cyst. However, studies reported early fluid reaccumulation and relative high recurrence rates of cyst growth after aspiration sclerotherapy ultimately leading to re-interventions. In this respect, somatostatin analogues are promising agents known for its volume reducing effect in patients with polycystic liver disease.

In this study the investigators want to evaluate the effect of combining aspiration sclerotherapy with the multi-receptor binding, long-acting somatostatin analogue Pasireotide.

The investigators hypothesize that administrating pasireotide before and after aspiration sclerotherapy could prevent early fluid reaccumulation and thereby result in a greater reduction of cyst diameter. Moreover, the investigators expect a lower rate of cyst recurrence and subsequently lower need for re-interventions.

Detailed Description

Not available

Study Timeline

• Study Start: 2013-12
• Study First Submitted: 2014-01-06
• Study First Submitted QC: 2014-01-27
• Study First Posted: 2014-01-29
• Primary Completion: 2015-11
• Study Completion: 2016-04
• Status Verified: 2016-05
• Last Update Submitted: 2016-05-03
• Last Update Posted: 2016-05-04

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 34

Inclusion Criteria

• All patients who are diagnosed with a dominant liver cyst with an indication for aspiration and sclerotherapy are suitable for inclusion in this study.

In order to be eligible to participate in this study, a subject must meet all of the following criteria:

• Age 18 - 70 years
• Indication for aspiration and sclerotherapy
• Providing informed consent

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Exclusion Criteria

A potential subject who meets any of the following criteria will be excluded from participation in this study

ASPIRATION SCLEROTHERAPY RELATED EXCLUSION CRITERIA:

1. Signs of cyst bleeding on ultrasound

2. Signs of cyst infection (elevated CRP and/or leukocytes or temperature exceeding 38 degrees with the exclusion of a different focus)

3. Cyst < 5 cm

4. Coagulopathy (INR > 2 or platelets < 80 x 10^9)

5. Severe co-morbidity contraindicating anesthesia (i.e. ASA 4 classification)

   SOMATOSTATIN TREATMENT RELATED EXCLUSION CRITERIA:

6. Patients with a known hypersensitivity to SST analogues or any component of the pasireotide LAR or SQ formulations

7. Pregnant or nursing women

8. Symptomatic cholecystolithiasis

9. QT interval related exclusion criteria:

   • 9.1 Known (congenital) long QT syndrome or QTcF at screening 470 msec
   • 9.2 Family history of long QT syndrome or idiopathic sudden death
   • 9.3 Uncontrolled or significant cardiac disease including recent myocardial infarction, congestive heart failure, unstable angina or sustained and/or clinically significant cardiac arrhythmias (e.g. bradycardia)
   • 9.4 Risk factors for torsades de pointes: hypokalemia, hypomagnesemia, hypocalcaemia, cardiac failure, clinically significant/symptomatic bradycardia, or high grade AV block
   • 9.5 Patients with concomitant disease(s) that could prolong QT such as autonomic neuropathy (caused by diabetes, or Parkinson's disease), HIV, cirrhosis, uncontrolled hypothyroidism or cardiac failure
   • 9.6 Taking anti-arrhythmic medicinal products or other substances that are known to lead to QT prolongation

10. Uncontrolled diabetes as defined by HbA1C > 64 mmol/ml despite adequate therapy

11. History of pancreatitis

12. Non-malignant medical illnesses that are uncontrolled or whose control may be jeopardized by the treatment with this study treatment

    FURTHERMORE:

13. Use of oral contraception or estrogen supplementation

14. Intervention (i.e. aspiration with or without sclerotherapy or surgical intervention) within six months before baseline

15. Treatment with somatostatin analogues within six months before baseline

16. Any current or prior medical condition that may interfere with the conduct of the study or the evaluation of its results in the opinion of the investigator

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Study & Design

• Study Type: INTERVENTIONAL
• Study Design: PARALLEL

Arm && Interventions

Group	Intervention	Description
Experimental: Pasireotide LAR 60 mg	Aspiration sclerotherapy	The subjects will be randomized (1:1) into two groups. Both groups will undergo aspiration sclerotherapy following the standard procedure. The intervention group will additionally receive two injections of 60 mg pasireotide long-acting release (LAR) intramuscularly: the first injection 14 days before and the second injection 14 days after the intervention.
Experimental: Pasireotide LAR 60 mg	Pasireotide LAR 60 mg	The subjects will be randomized (1:1) into two groups. Both groups will undergo aspiration sclerotherapy following the standard procedure. The intervention group will additionally receive two injections of 60 mg pasireotide long-acting release (LAR) intramuscularly: the first injection 14 days before and the second injection 14 days after the intervention.
Placebo	Placebo	Patients in the placebo arm will receive two injections of saline solution corresponding to the scheme of the intervention group.
Placebo	Aspiration sclerotherapy	Patients in the placebo arm will receive two injections of saline solution corresponding to the scheme of the intervention group.

Primary Outcome Measures

Name	Time	Method
Proportional diameter change	4 weeks	Proportional change (%) in cyst diameter measured by ultrasound 4 weeks after aspiration sclerotherapy.

Secondary Outcome Measures

Name	Time	Method
Proportional (%) and absolute cyst reduction (cm) after 12 weeks	12 weeks	Proportional (%) and absolute change in cyst diameter measured by ultrasound 12 weeks after aspiration sclerotherapy.
Symptomatic change and health-related quality of life	4, 12 weeks and 24 weeks	Assessment of gastro-intestinal symptoms and health-related quality of life by the GIS- and SF-36 questionnaire respectively
Proportional (%) and absolute cyst reduction (cm) after 24 weeks	24 weeks	Long term proportional (%) and absolute change in cyst diameter measured by ultrasound 24 weeks after aspiration sclerotherapy.
Absolute reduction (cm) hepatic cyst	4 weeks	Absolute change in cyst diameter measured by ultrasound 4 weeks after aspiration sclerotherapy.
Proportion cyst recurrence	12 weeks	\> 80% of its original diameter
Safety	At week 2, week 4, week 6, week 14 and week 26 after first Pasireotide injection	Any complications or adverse events reported during procedure or follow-up

Trial Locations

Locations (1)

Radboud University Nijmegen Medical Center; Department of Gastroenterology & Hepatology; 🇳🇱 Nijmegen, Netherlands