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

• ClinicalTrials.gov Identifier: NCT05500157
• Recruitment Status: Not yet recruiting
• First Posted: August 12, 2022
• Last Update Posted: August 12, 2022
• Sponsor: Radboud University Medical Center
• Information provided by (Responsible Party): Radboud University Medical Center

Study Description

Brief Summary:

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.

Condition or disease	Intervention/treatment	Phase
Liver Cyst; Polycystic Liver Disease; Autosomal Dominant Polycystic Kidney; Autosomal Dominant Polycystic Liver Disease	Procedure: aspiration sclerotherapy versus laparoscopic fenestration	Not Applicable

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 Design

• Study Type: Interventional (Clinical Trial)
• Estimated Enrollment: 70 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: None (Open Label)
• Primary Purpose: Treatment
• Official Title: Assessment of Treatment With Laparoscopic Fenestration or Aspiration Sclerotherapy for Large Symptomatic Hepatic Cysts (ATLAS): a Randomized Clinical Trial.
• Estimated Study Start Date: October 1, 2022
• Estimated Primary Completion Date: October 1, 2023
• Estimated Study Completion Date: October 1, 2024

Arms and Interventions

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

Outcome Measures

Primary Outcome Measures :

1. PLD-Q 4 weeks [ Time Frame: 4 weeks after the procedure ]
   Comparison of PLD-Q scores 4 weeks after the procedure, adjusted for baseline PLD-Q score.

Secondary Outcome Measures :

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

Eligibility Criteria

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

Criteria

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).

Contacts and Locations

Contacts

Contact: Joost P.H. Drenth; +31 24 3619190; joostphdrenth@cs.com

Contact: Thijs Barten; +31 24 8186542; thijs.rm.barten@radboudumc.nl

Sponsors and Collaborators

Radboud University Medical Center

Investigators

• Principal Investigator: Joost P.H. Drenth; Radboud University Medical Center

More Information

• Responsible Party: Radboud University Medical Center
• ClinicalTrials.gov Identifier: NCT05500157
• Other Study ID Numbers: 2020-7134
• First Posted: August 12, 2022
• Last Update Posted: August 12, 2022
• Last Verified: May 2022

Individual Participant Data (IPD) Sharing Statement:

• Plan to Share IPD: Yes
• Plan Description: Individual participant data are available to other researchers for clinical research purposes upon reasonable request to the principal investigator
• Supporting Materials: Study Protocol; Statistical Analysis Plan (SAP); Informed Consent Form (ICF); Clinical Study Report (CSR); Analytic Code
• Time Frame: Study data will be provided upon reasonable request with the principal investigator
• Access Criteria: Study data will be provided upon reasonable request with the principal investigator

• Studies a U.S. FDA-regulated Drug Product: No
• Studies a U.S. FDA-regulated Device Product: No

Keywords provided by Radboud University Medical Center:

polycystic liver disease; aspiration sclerotherapy; fenestration

Additional relevant MeSH terms:

Cysts; Arthrogryposis; Liver Diseases; Polycystic Kidney Diseases; Polycystic Kidney, Autosomal Dominant; Digestive System Diseases; Neoplasms; Pathological Conditions, Anatomical; Joint Diseases; Musculoskeletal Diseases; Muscular Diseases; Musculoskeletal Abnormalities; Congenital Abnormalities; Kidney Diseases, Cystic; Kidney Diseases; Urologic Diseases; Abnormalities, Multiple; Ciliopathies; Genetic Diseases, Inborn