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

• ClinicalTrials.gov Identifier: NCT02048319
• Recruitment Status: Completed
• First Posted: January 29, 2014
• Last Update Posted: May 4, 2016
• Sponsor: Radboud University Medical Center
• Information provided by (Responsible Party): Radboud University Medical Center

Tracking Information

• First Submitted Date: January 6, 2014
• First Posted Date: January 29, 2014
• Last Update Posted Date: May 4, 2016
• Study Start Date: December 2013
• Actual Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)

Current Primary Outcome Measures (submitted: January 27, 2014)

Proportional diameter change [ Time Frame: 4 weeks ]

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

• Original Primary Outcome Measures: Same as current

Current Secondary Outcome Measures (submitted: November 5, 2014)

• Absolute reduction (cm) hepatic cyst [ Time Frame: 4 weeks ]
  Absolute change in cyst diameter measured by ultrasound 4 weeks after aspiration sclerotherapy.
• Proportional (%) and absolute cyst reduction (cm) after 12 weeks [ Time Frame: 12 weeks ]
  Proportional (%) and absolute change in cyst diameter measured by ultrasound 12 weeks after aspiration sclerotherapy.
• Proportion cyst recurrence [ Time Frame: 12 weeks ]
  > 80% of its original diameter
• Symptomatic change and health-related quality of life [ Time Frame: 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
• Safety [ Time Frame: 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
• Proportional (%) and absolute cyst reduction (cm) after 24 weeks [ Time Frame: 24 weeks ]
  Long term proportional (%) and absolute change in cyst diameter measured by ultrasound 24 weeks after aspiration sclerotherapy.

Original Secondary Outcome Measures (submitted: January 27, 2014)

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

• Current Other Pre-specified Outcome Measures: Not Provided
• Original Other Pre-specified Outcome Measures: Not Provided

Descriptive Information

• Brief Title: 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.

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 Provided
• Study Type: Interventional
• Study Phase: Phase 3
• Study Design: Allocation: Randomized; Intervention Model: Parallel Assignment; Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor); Primary Purpose: Treatment
• Condition: Symptomatic Dominant Liver Cyst

Intervention

• Drug: Pasireotide LAR 60 mg
  Pasireotide long acting release, intramuscular injection
  Other Name: Pasireotide long acting release, intramuscular injection
• Procedure: Aspiration sclerotherapy
  Percutaneous drainage of the hepatic cyst with subsequent ethanol instillation
  Other Name: Drainage with subsequent ethanol instillation
• Drug: Placebo
  Saline solution, injected as placebo
  Other Name: Saline solution

Study Arms

• Experimental: Experimental: 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.
  Interventions:

  • Drug: Pasireotide LAR 60 mg
  • Procedure: Aspiration sclerotherapy
• Placebo Comparator: Placebo
  Patients in the placebo arm will receive two injections of saline solution corresponding to the scheme of the intervention group.
  Interventions:

  • Procedure: Aspiration sclerotherapy
  • Drug: Placebo

• Publications *: 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.

Recruitment Information

• Recruitment Status: Completed
• Actual Enrollment (submitted: January 27, 2014): 34
• Original Estimated Enrollment: Same as current
• Actual Study Completion Date: April 2016
• Actual Primary Completion Date: November 2015 (Final data collection date for primary outcome measure)

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

Sex/Gender

• Sexes Eligible for Study: All

• Ages: 18 Years to 70 Years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Contacts: Contact information is only displayed when the study is recruiting subjects
• Listed Location Countries: Netherlands

Administrative Information

• NCT Number: NCT02048319
• Other Study ID Numbers: JDTW45115; 2013-003168-29 ( EudraCT Number )
• Has Data Monitoring Committee: Yes
• U.S. FDA-regulated Product: Not Provided
• IPD Sharing Statement: Not Provided
• Current Responsible Party: Radboud University Medical Center
• Original Responsible Party: Same as current
• Current Study Sponsor: Radboud University Medical Center
• Original Study Sponsor: Same as current
• Collaborators: Not Provided
• Investigators: Not Provided
• PRS Account: Radboud University Medical Center
• Verification Date: May 2016