This study has been transitioned to CTIS with ID 2024-512040-28-01 check the CTIS register for the current data. To assess the incidence of post-TIPS OHE within the first three months after prophylactic administration of lactulose and rifaximin…
ID
Source
Brief title
Condition
- Other condition
Synonym
Health condition
hepatische encefalopathie
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Primary endpoint is the development of OHE within three months after TIPS
placement determined by the West Haven criteria.
substudy 1:
Primary objective of this ancillary study is to assess the effect of TIPS
placement on microbiota-host interaction based on the following assessments at
screening, day of TIPS placement, month 3 (end of study medication treatment)
and month 12:
- 16s rRNA based analysis of microbiota in stool
- 16s rRNA based analysis of microbiota in saliva
- Circulating biomarkers for inflammatory, circulatory and endothelial function.
substudy 2:
- To compare the activation status, immunological and metabolic function
of circulating monocytes/macrophages obtained from patients with alcoholic
liver cirrhosis (ALD).
Secondary outcome
Secondary endpoints are 90 day mortality;
development of a second episode of OHE within the first three months;
development of OHE in the period between three and twelve months after TIPS
placement;
development of MHE between TIPS placement and twelve months after placement;
time to development of OHE or MHE episode(s)
the increase of the PHES and simplified one minute animal naming test (S-ANT1)
at week 4, week 12 and week 52, compared to baseline.
the change in Liver Frailty Index score at week 12 and week 52, compared to
baseline
Differences in molecular composition of peripheral / portal blood samples at
TIPS placement.
Differences in molecular composition of peripheral blood samples at baseline,
week 12 and week 52.
Furthermore, quality of life will be assessed by the Liver Disease Symptom
Index 2.0 (LDSI 2.0) and EQ-5D-5L questionnaires at baseline, week 12 and week
52.
Economic evaluation.
substudy 1:
- to assess the relationship between post-TIPS hepatic encephalopathy and
microbiota composition.
- to assess the relationship between post-TIPS hepatic encephalopathy and
inflammatory, circulatory and endothelial function respectively.
- to assess the relationship between post-TIPS acute decompensation/ACLF or
mortality at short (3 months) and long term (< 12 months) and microbiota
composition.
- to assess the relationship between post-TIPS acute decompensation/ACLF or
mortality at short (3 months) and long term (< 12 months) and inflammatory,
circulatory and endothelial function respectively.
substudy 2:
* Identify the levels of bacterial products, in the portal and systemic blood
from patients with ALD.
* Identify the nature and levels of inflammatory cytokines reaching the liver
from the gut in patients with decompensated liver disease undergoing TIPS for
intractable ascites
* To determine the pre and post TIPS immunological factors that may be
predictive of encephalopathy following TIPS placement.
* To determine the activation status, cytokines responses, immunological- and
metabolic function by circulating monocytes present in the peripheral blood of
patients admitted with acute alcoholic hepatitis and acute- on- chronic liver
failure and how these individual responses may correlate with survival.
* To follow up patients longitudinally and identify a set of parameters and
read-outs that can predict patient outcome.
Background summary
Hepatic encephalopathy (HE) is a major and common complication in patients with
liver cirrhosis. HE can be classified in the extensive range of neurocognitive
deterioration as minimal HE (MHE), covert HE (grade I), or overt HE (OHE, grade
II-IV). Liver cirrhosis is the most common cause of portal hypertension (PH).
Patients who develop complications of PH, like variceal bleeding or refractory
ascites, can benefit from a Transjugular Intrahepatic Portosystemic Shunt
(TIPS) placement. Unfortunately, post-TIPS HE is a common and often severe
complication. Incidence of new onset or worsening of HE after TIPS is
approximately 20-45%. Currently there is no strategy to prevent post-TIPS HE.
Study objective
This study has been transitioned to CTIS with ID 2024-512040-28-01 check the CTIS register for the current data.
To assess the incidence of post-TIPS OHE within the first three months after
prophylactic administration of lactulose and rifaximin versus placebo in
patients who undergo Transjugular Intrahepatic Portosystemic Shunt (TIPS)
placement.
Study design
A multicentre, randomized, placebo-controlled, double blind study.
Intervention
Rifaximin 550mg b.i.d. will be prescribed, in combination with a starting dose
of 25mL lactulose b.i.d. (or a previous prescribed dose) and further dependent
on the amount of daily bowel movements, with the objective not to exceed more
than two soft stools per day.
Intervention will start 72 hours before TIPS placement, and will last till
three months after TIPS placement.
The control group will receive placebo in combination with lactulose (as
described above).
Study burden and risks
Since study visits are combined with regular visits, participants have a
minimal extra burden of this study. Blood withdrawl will be in combination with
regular sampling. Psycomotoric tests are all non-invasive.
Study medication is safe and adverse effects of lactulose are highly dosage
dependent and can be adjusted properly.
Amsterdam 1105AZ
NL
Amsterdam 1105AZ
NL
Listed location countries
Age
Inclusion criteria
1. Elective TIPS placement for refractory ascites or recurrent variceal
bleeding:
* Recurrent tense ascites and one or more of the following criteria:
i. Not responding to the maximal dose of diuretics (400mg spironolactone and
160mg furosemide).
ii. Kidney insufficiency (Creatinine > 135 umol/L) induced by diuretics.
iii. Electrolyte disturbances (Sodium < 125 mmol/L, Potassium > 5.5 mmol/L)
induced by diuretics.
iv. Not tolerating higher dose of diuretics. (e.g. because of subjective side
effects like muscle cramps).
* (Recurrent) variceal bleeding, not responsive to treatment with endoscopic
band ligation and/or beta-blockers, with a high risk of failure of endoscopic
treatment:
i. Patients with a variceal bleeding and Child-Pugh C (10-13 points) cirrhosis
ii. Patients with a variceal bleeding, Child-Pugh B and an active bleeding
during endoscopy
2. Age * 18 years
3. Confirmed liver cirrhosis as documented by liver biopsy, elastography (e.g.
Fibroscan) or combination of usual radiological and biochemical criteria.
4. Signed informed consent
Exclusion criteria
1. Any absolute contraindications for TIPS placement:
a. History of hepatic encephalopathy grade II-IV without precipitating factor
b. Heart failure NYHA * grade 3
c. Hepatocellular carcinoma (multifocal or large or centrally located)
d. Systemic infection / sepsis
e. Severe pulmonary hypertension
f. Unrelieved bile duct obstruction
g. Technically not feasible
h. Poor liver function (MELD score > 20)
2. Use of ciclosporin
3. Life-threating variceal bleeding with emergency TIPS placement
4. Age > 80 years
5. Non-cirrhotic portal hypertension
6. Portal vein thrombosis (main trunk)
7. Current or recent (<3 months) use of rifaximin
8. Overt neurologic diseases such as Alzheimer*s disease, Parkinson*s disease
9. Pregnant or breastfeeding women
10. Patients refusing or unable to sign informed consent
Design
Recruitment
Medical products/devices used
Kamer G4-214
Postbus 22660
1100 DD Amsterdam
020 566 7389
mecamc@amsterdamumc.nl
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| EU-CTR | CTIS2024-512040-28-01 |
| EudraCT | EUCTR2018-004323-37-NL |
| ClinicalTrials.gov | NCT04073290 |
| CCMO | NL68205.018.18 |