Clinical trial NCT02048319: Efficacy of Combining Pasireotide With Aspiration Sclerotherapy to Improve Volume Reduction of Hepatic Cysts
Official title: Assessing Efficacy of Combining Pasireotide With Aspiration Sclerotherapy to Improve Volume Reduction of Dominant Hepatic Cysts: a Randomized, Double-blind, Placebo-controlled Clinical Trial.
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE3
Conditions: Symptomatic Dominant Liver Cyst
Keywords: Liver cyst
Hepatic cyst
Symptomatic
Aspiration sclerotherapy
Lead sponsor: Radboud University Medical Center
Sponsor class: OTHER
First posted: 2014-01-29
Enrollment: 34
Sex: ALL
Minimum age (years): 18
Maximum age (years): 70
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

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.


Eligibility criteria: 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

Primary outcomes:
measure: Proportional diameter change
timeFrame: 4 weeks
Secondary outcomes:
measure: Absolute reduction (cm) hepatic cyst
timeFrame: 4 weeks
measure: Proportional (%) and absolute cyst reduction (cm) after 12 weeks
timeFrame: 12 weeks
measure: Proportion cyst recurrence
timeFrame: 12 weeks
measure: Symptomatic change and health-related quality of life
timeFrame: 4, 12 weeks and 24 weeks
measure: Safety
timeFrame: At week 2, week 4, week 6, week 14 and week 26 after first Pasireotide injection
measure: Proportional (%) and absolute cyst reduction (cm) after 24 weeks
timeFrame: 24 weeks
Other outcomes:
Locations:
city: Nijmegen
country: Netherlands
facility: Radboud University Nijmegen Medical Center; Department of Gastroenterology & Hepatology
Study officials:
References:
citation: Wijnands TF, Gevers TJ, Kool LJ, Drenth JP. Aspiration sclerotherapy combined with pasireotide to improve reduction of large symptomatic hepatic cysts (SCLEROCYST): study protocol for a randomized controlled trial. Trials. 2015 Mar 7;16:82. doi: 10.1186/s13063-015-0607-3.