Assessment of Treatment With Laparoscopic Fenestration or Aspiration Sclerotherapy for Large Symptomatic Hepatic Cysts (ATLAS)

Assessment of Treatment With Laparoscopic Fenestration or Aspiration Sclerotherapy for Large Symptomatic Hepatic Cysts (ATLAS): a Randomized Clinical Trial.

Patients with large hepatic cysts (> 5cm) may develop symptoms. These can be captured with the polycystic liver disease questionnaire (PLD-Q). Treatment of large hepatic cysts consists of aspiration sclerotherapy or laparoscopic fenestration.

The safety and efficacy of both procedures has been explored in two recent systematic reviews yet no evident conclusion regarding superiority of either procedure could be drawn.

The main objective of the ATLAS trial is to compare laparoscopic fenestration and aspiration sclerotherapy in patients with large symptomatic hepatic cysts on patient-reported outcomes.

Study Overview

• Status: Recruiting
• Conditions: Autosomal Dominant Polycystic Kidney; Polycystic Liver Disease; Liver Cyst; Autosomal Dominant Polycystic Liver Disease
• Intervention / Treatment: Procedure: aspiration sclerotherapy versus laparoscopic fenestration

Detailed Description

Rationale: Patients with large hepatic cysts(>5cm) may develop symptoms due to distention of Glisson's capsule and/or compression on other abdominal organs. Frequently reported symptoms include abdominal pain, early satiety, nausea, and dyspnea. These symptoms can be captured in the disease-specific Polycystic Liver Disease Questionnaire (PLD-Q), a validated instrument. The treatment of symptomatic liver cysts is aimed to improve symptoms and quality of life by reducing cyst volume. There are two procedures available to treat symptomatic liver cysts: percutaneous aspiration sclerotherapy and laparoscopic fenestration.

In aspiration sclerotherapy, fluid is evacuated from the liver cyst and subsequently the cyst lining is exposed to a sclerosing agent for a limited period of time. Sclerotherapy causes temporary recurrence of cyst fluid after drainage, but subsequently results in a steady decrease of cyst volume in the majority of patients.

In laparoscopic fenestration the liver is exposed through laparoscopic surgery. In this procedure the cyst is punctured and drained followed by resection of extra-hepatic cyst wall.

The safety and efficacy of aspiration sclerotherapy and laparoscopic fenestration have been explored in two recent systematic reviews. No evident conclusion could be drawn because of the retrospective study design in the vast majority of the studies and the heterogeneity among these. A randomized controlled trial is warranted to identify the possible differences in safety and efficacy in aspiration sclerotherapy and laparoscopic fenestration.

Hypothesis: The investigators expect patients treated with laparoscopic fenestration to have better clinical outcome; i.e. a lower PLD-Q score, compared to aspiration sclerotherapy, when measured 4 weeks after the procedure. The investigators expect this difference to become smaller over time (after 6 and 12 months), with loss of statistical significance.

Objective: The main objective is to compare laparoscopic fenestration and aspiration sclerotherapy in patients with large symptomatic hepatic cysts on patient-reported outcomes. This information can be used to assess cost-effectiveness in both treatments.

Study design: A prospective, randomized clinical superiority trial in which patients will be randomized 1:1 to one of the treatment arms. Patients will be followed for 1 year.

Study population: All patients ≥18 years who are diagnosed with a dominant, simple hepatic cyst (>5 cm in diameter), that are symptomatic (PLD-Q score ≥20) and have an indication for treatment (both aspiration sclerotherapy and laparoscopic fenestration) are suitable for inclusion in this study. Only patients that are eligible for both treatments can be included in this study. In particular, patients with multiple cysts (>20 cysts of >1.5 cm) will be excluded as surgery leads to more complications in these patients.

Intervention: Patients will be randomly allocated to either aspiration sclerotherapy or laparoscopic fenestration. Both procedures are performed according to the standard Radboudumc protocols. Aspiration sclerotherapy consists of ultrasound-guided, percutaneous drainage of the cyst with subsequent sclerosation with ethanol. Laparoscopic fenestration consists of standard abdominal laparoscopy in which the large cyst(s) are drained and deroofed.

Main study parameters: The main study parameter is the PLD-Q score at 4 weeks after treatment. Secondary parameters are among others: PLD-Q score at baseline, 6 months and 12 months; liver volume (CT) at baseline and 4 weeks; cyst volume (ultrasound) at baseline, 4 weeks, 6 months and 12 months; complications according to Clavien-Dindo; admission duration, recurrence and re-intervention rates.

• Study Type: Interventional
• Enrollment (Anticipated): 70
• Phase: Not Applicable

Contacts and Locations

• Study Contact: Name: Joost P.H. Drenth; Phone Number: +31 24 3619190; Email: joostphdrenth@cs.com
• Study Contact Backup: Name: Thijs Barten; Phone Number: +31 24 8186542; Email: thijs.rm.barten@radboudumc.nl

Study Locations

• Netherlands
  • Gelderland
    • Nijmegen, Gelderland, Netherlands, 6500 HB
      • Recruiting
      • Radboudumc University Medical Center
      • Contact: Radboudumc University M Center; Phone Number: +31644107787; Email: joost.drenth@radboudumc.nl

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 75 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Age ≥18 years

• Hepatic cyst characteristics:

  • Large (>5 cm),
  • Symptomatic (PLD-Q score ≥20),
  • Non-parasitic on imaging (US/CT/MRI)
  • Non-neoplastic on imaging (US/CT/MRI)
• Providing informed consent

Exclusion Criteria:

• Clinical indication of a complicated hepatic cyst (cyst rupture or active cyst infection)
• Cyst is not laparoscopically accessible for surgery
• Cyst is not percutaneously (ultrasound-guided) accessible for aspiration
• More than 20 cysts of >1.5 cm
• Age above 75 years
• ASA IV
• ECOG score >1
• Aspiration sclerotherapy or laparoscopic fenestration of hepatic cysts was performed in the last 6 months.
• Severe renal impairment (eGFR < 30 ml/min/1,73 m2)
• Coagulopathy (spontaneous INR >2 or platelet count < 80 x 109/l)
• Radiologic contrast allergy
• Pregnancy
• 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 (e.g. inability to fill out questionnaires).

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: None (Open Label)

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Active Comparator: Aspiration sclerotherapy; Aspiration sclerotherapy is a percutaneous procedure that evacuates fluid from the liver cyst and subsequently exposes cyst lining to a sclerosing agent (e.g. ethanol, minocycline) for a limited period of time.	Procedure: aspiration sclerotherapy versus laparoscopic fenestration; See arm description
Active Comparator: Laparoscopic Fenestration; Laparoscopic fenestration exposes the liver through laparoscopic surgery. During this procedure the cyst is punctured and drained followed by resection of the extra-hepatic cyst wall	Procedure: aspiration sclerotherapy versus laparoscopic fenestration; See arm description

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PLD-Q 4 weeks	Comparison of PLD-Q scores 4 weeks after the procedure, adjusted for baseline PLD-Q score.	4 weeks after the procedure

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
PLD-Q score 1, 6 and 12 months after intervention	PLD-Q score at 1, 6 and 12 months after intervention, adjusted for baseline	up to 12 months
PLD-Q invididual symptoms	PLD-Q individual symptom scores at 1, 6 and 12 months after intervention, compared to baseline	up to 12 months
SF-36 MCS	SF-36 Mental Component Score at 1, 6 and 12 months after intervention, adjusted to baseline	up to 12 months
SF 36 PCS	SF-36 Physical Component Score at 1, 6 and 12 months after intervention, adjusted to baseline	up to 12 months
EQ-5D-5L	EQ-5D-5L score at 1, 6 and 12 months after intervention, adjusted to baseline	up to 12 months
Liver and cyst volume	Liver and cyst volume with CT before and 12 months after the intervention	up to 12 months
Liver and cyst volume at recurrence	Liver and cyst volume in cases of recurrence of symptoms	up to 12 months
Cyst volume with US	Cyst volume with ultrasound, at baseline and 1, 6 and 12 months after intervention.	up to 12 months
Adverse events	Adverse events (according to Clavien-Dindo)	up to 12 months
Technical success	Technical success	periprocedural
Hospital stay	Hospital stay in days	periprocedural
Re-intervention rates	Re-intervention rates during 12 months follow-up.	up to 12 months
Cost-effectiveness iPCQ	Cost-effectiveness of both procedures iPCQ 1, 6 and 12 months after intervention, adjusted for baseline	up to 12 months
Cost-effectiveness iMCQ	Cost-effectiveness of both procedures iMCQ 1, 6 and 12 months after intervention, adjusted for baseline	up to 12 months

Collaborators and Investigators

• Sponsor: Radboud University Medical Center
• Investigators: Principal Investigator: Joost P.H. Drenth, Radboud University Medical Center

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2022
• Primary Completion (Anticipated): October 1, 2023
• Study Completion (Anticipated): October 1, 2024

Study Registration Dates

• First Submitted: May 6, 2022
• First Submitted That Met QC Criteria: August 11, 2022
• First Posted (Actual): August 12, 2022

Study Record Updates

• Last Update Posted (Actual): April 5, 2023
• Last Update Submitted That Met QC Criteria: April 2, 2023
• Last Verified: May 1, 2022

More Information

Terms related to this study

• Keywords: polycystic liver disease; aspiration sclerotherapy; fenestration
• Additional Relevant MeSH Terms: Digestive System Diseases; Neoplasms; Kidney Diseases; Urologic Diseases; Congenital Abnormalities; Genetic Diseases, Inborn; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Pathological Conditions, Anatomical; Musculoskeletal Abnormalities; Abnormalities, Multiple; Kidney Diseases, Cystic; Ciliopathies; Liver Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Arthrogryposis; Cysts
• Other Study ID Numbers: 2020-7134

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: Individual participant data are available to other researchers for clinical research purposes upon reasonable request to the principal investigator
• IPD Sharing Time Frame: Study data will be provided upon reasonable request with the principal investigator
• IPD Sharing Access Criteria: Study data will be provided upon reasonable request with the principal investigator
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; SAP; ICF; ANALYTIC_CODE; CSR

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No