Clinical trial NCT05037643: Pre-emptive Transjugular Intrahepatic Portosystemic Shunt (TIPS) in Cystic Fibrosis Related Liver Disease
Official title: Pre-emptive Transjugular Intrahepatic Portosystemic Shunt (TIPS) in Pediatric Patients With Cystic Fibrosis Related Liver Disease and Non-cirrhotic Portal Hypertension
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Cystic Fibrosis Liver Disease
Portal Hypertension Due to Cystic Fibrosis (Disorder)
Portal Hypertension, Noncirrhotic
Keywords: Transjugular Intrahepatic Portosystemic Shunt
Gastrointestinal bleeding
Hypersplenism
Lead sponsor: University Hospital, Ghent
Sponsor class: OTHER
First posted: 2021-09-08
Enrollment: 5
Sex: ALL
Maximum age (years): 18
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective single-arm study
Primary purpose: PREVENTION

Brief summary: Portal hypertension (PHT) and its sequelae are the most clinically important manifestation in cystic fibrosis related liver disease (CFLD), with end-stage liver failure as a late and rare manifestation. The aim is to evaluate the safety and efficacy of a pre-emptive Transjugular Intrahepatic Portosystemic Shunt (TIPS) for the prophylaxis of variceal bleeding in pediatric CFLD patients with subclinical non-cirrhotic portal hypertension (NCPH)

Detailed description: Cystic fibrosis (CF) is the most frequent autosomal recessive disorder in Caucasians caused by a mutation in the cystic fibrosis transmembrane conductance regulator gene. Cystic Fibrosis associated Liver Disease (CFLD) is a well-known complication and includes a wide range of hepatobiliary diseases. The clinical outcome in CFLD is largely determined by PHT and its sequelae. Variceal bleeding is the most feared complication. Currently, there is no medical therapy to delay or reverse clinically established CFLD.Treatment focuses on screening for and managing the complications of portal hypertension and optimizing nutritional status. Eventually, liver transplantation (LT) is an effective therapeutic option for CF patients with end-stage liver failure, treatment resistant, and complicated portal hypertension.

TIPS placement is a well-established procedure for portal vein decompression in adults. In retrospective case studies of severe CFLD cirrhosis in pediatric populations, TIPS has been proven a feasible option in acute or refractory variceal bleeding and as a bridge to LT. In CFLD patients, little data are available on the long-term outcome of treatments to mitigate PHT. In this trial, the primary aim was to evaluate the safety and efficacy of a pre-emptive TIPS for the prophylaxis of variceal bleeding in non-cirrhotic CFLD with early PHT. The secondary aim was to investigate the long-term clinical outcome of a pre-emptive TIPS and in more particular, whether TIPS might effectively postpone LT.

Eligibility criteria: Inclusion Criteria:

* Cystic fibrosis
* Liver disease detected by an abnormal physical examination (hepatomegaly or splenomegaly, confirmed on US), abnormalities of liver function tests (increase of AST, ALT, GGT levels above the upper normal limits) or ultrasonographic evidence of liver involvement (US liver score ≥ 5).
* Indirect signs of portal hypertension on Doppler US
* Progressive portal hypertension / liver disease on bi-monthly follow-up, evaluated by physical examination, blood analysis and US

Exclusion Criteria:

* Cirrhosis on biopsy
* Symptomatic portal hypertension (Portosytemic pressure gradient \> 10 mmHg)

Primary outcomes:
measure: Variceal bleeding
timeFrame: Through study completion, an average of 10 year
Secondary outcomes:
measure: Hypersplenism
timeFrame: Through study completion, an average of 10 year
Other outcomes:
measure: Liver transplant/splenectomy-free survival
timeFrame: Through study completion, an average of 10 year
measure: Model for end-stage liver disease (MELD) score
timeFrame: Through study completion, an average of 10 year
measure: Body Mass Index (BMI) for age Z-score
timeFrame: Through study completion, an average of 10 year
measure: Length for age Z-score
timeFrame: Through study completion, an average of 10 year
Locations:
Study officials:
affiliation: University Ghent Hospital
name: Luc Defreyne, M.D., Ph.D
role: PRINCIPAL_INVESTIGATOR
References: