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

Radboud University Medical Center

Status and phase: Completed; Phase 3

Conditions: Symptomatic Dominant Liver Cyst

Treatments: Procedure: Aspiration sclerotherapy; Drug: Pasireotide LAR 60 mg; Drug: Placebo

Study type: Interventional

Funder types: Other

Identifiers

NCT02048319

JDTW45115

2013-003168-29 (EudraCT Number)

Details and patient eligibility

About

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.

Enrollment: 34 patients

Sex: All

Ages: 18 to 70 years old

Volunteers: No Healthy Volunteers

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

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Parallel Assignment

Masking: Quadruple Blind

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34 participants in 2 patient groups, including a placebo group

Experimental: Pasireotide LAR 60 mg

Experimental group

Description:

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.

Treatment:

Procedure: Aspiration sclerotherapy

Drug: Pasireotide LAR 60 mg

Placebo

Placebo Comparator group

Description:

Patients in the placebo arm will receive two injections of saline solution corresponding to the scheme of the intervention group.

Treatment:

Drug: Placebo

Procedure: Aspiration sclerotherapy