Liver CirrhosisNCT03005444
Anticoagulation for Advanced Cirrhotic Patients After TIPS
A study testing Rivaroxaban in people with Liver Cirrhosis, run by Air Force Military Medical University, China at 11 sites in China.
Trial summary
Recent studies demonstrated that liver cirrhosis was associated with a hypercoagulability state. Besides, bacterial translocation plays an important role in the pathogenesis and complications in patients with decompensated cirrhosis, including infections as well as hepatic encephalopathy and hepatorenal syndrome. Read more about this study
- Who is it for?
- Ages 18 to 75 years
- Conditions the study is for
- Liver Cirrhosis
- What is being tested?
- Rivaroxaban
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 254 participants
- Where
- 11 sitesChina
- Study dates
- 14 Jun 2017to 31 Dec 2024
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 75 years
- All sexes
- No healthy volunteers
- Adult, Older adult
All inclusion criteria must be met at the time of screening:
- Signed informed consent.
- Male or female patients with an age of 18 to 75 years
- Liver cirrhosis.
- History of variceal bleeding > 5 days
- Presence of ascites
- Successful TIPS
- Use of Viatorr stent
- Child-Pugh score within B7-C13
- Bilirubin level of 3 mg/dL or less (51.3 umol/L)
Patients who meet the following criteria at the time of screening will be excluded:
- Hepatocellular carcinoma or other intrahepatic/extrahepatic cancers.
- Spontaneous overt hepatic encephalopathy.
- Previous or current portal venous system thrombosis.
- Budd-Chiari syndrome.
- Known coagulation disorder besides liver cirrhosis.
- Severe thrombocytopenia <15,000 platelets/dl.
- Peptic ulcer disease in the last 6 months.
- Unstable angina or myocardial infarction (MI) within the past 6 months before randomization.
- Cardiac arrhythmias requiring anti-arrhythmic therapy (beta blockers or digoxin are permitted).
- Uncontrolled hypertension.
- Prior liver transplantation or candidates for liver transplantation.
- History of shunting surgery or TIPS before randomization.
- Pregnancy or breastfeeding
- Poor compliance
- Participation in another clinical trial
- Close affiliation with the investigational site.
Trial locations and contacts
11 sites in 1 country.
11 sites in 1 country
China11 sites, 10 recruiting
- Recruiting
The Third Affiliated Hospital of Sun Yat-sen University
Guangzhou, Guangdong
- Recruiting
Nanfang Hospital Affiliated to Southern Medical University
Guanzhou, Guangdong
- Recruiting
The First Affiliated Hospital of Zhejiang University
Hangzhou, Zhejiang
- Recruiting
Provincial Hospital Affiliated to Shandong University
Jinan, Shandong
- Recruiting
The Second Affiliated Hospital of Kunming Medical University
Kunming, Yunnan
- Recruiting
The first affiliated hospital of Nanchang university
Nanchang, Jiangxi
- Recruiting
The Affiliated Nanjing Drum Tower Hospital of Nanjing University Medical School
Nanjing, Jiangsu
- Recruiting
The First Affiliated Hospital of Xinjiang Medical University
Ürümqi, Xinjiang
- Completed
The First Affiliated Hospital, Air Force Medical University
Xi'an, Shaanxi, 710032
- Recruiting
Xi'an International Medical Center Hospital
Xi'an, Shaanxi, 710100
Guohong Han, MD,Ph.D, 13991969930@126.com
Guohong Han, MD,Ph.D
- Recruiting
The First Affiliated Hospital of Xi'an Jiaotong University
Xi'an, Shaanxi
About this study
Official title: Anticoagulation for Development of Further Decompensation and Survival in Advanced Cirrhosis After Transjugular Intrahepatic Portosystemic Shunt: a Multicenter Randomized Controlled Study
Recent studies demonstrated that liver cirrhosis was associated with a hypercoagulability state. Besides, bacterial translocation plays an important role in the pathogenesis and complications in patients with decompensated cirrhosis, including infections as well as hepatic encephalopathy and hepatorenal syndrome.
A recent prospective study in a group of 70 patients with liver cirrhosis (Child B and C stages up to 10 points) who were randomized to receive enoxaparin for a year (n = 34) vs no intervention (n = 36) showed that anticoagulant treatment with enoxaparin is safe and effective, significantly reducing risk of PVT development and liver decompensation, markedly improving overall survival. This study provides exciting preliminary data regarding the potential use of prophylactic anticoagulation in improving clinical outcomes in cirrhosis, beyond the prevention of portal vein thrombosis. This study suggested that the effect was partly due to a direct effect of reducing BT and levels of proinflammatory cytokines. However, this study included few patients, was not double blind, and did not have a placebo group. Therefore, despite the spectacular results, the use of prophylactic anticoagulant therapy has not become routine practice in patients with cirrhosis and more studies are needed to assess the potential usefulness of anticoagulation in improving the prognosis of liver cirrhosis.
Read more
Transjugular intrahepatic portosystemic shunts (TIPS) are now routinely used to treat the complications of portal hypertension, such as variceal bleeding and refractory ascites. TIPS is the most effective method to prevent rebleeding, however, it is burdened with increased risk of hepatic encephalopathy and deterioration of liver function in patients with advanced cirrhosis. Notably, TIPS can not only relieve portal pressure but also can redirect the portal blood flow through the shunt directly into the systemic circulation which can cause systemic hemodynamic changes.
Given the preliminary data suggesting a beneficial effect of prophylactic anticoagulation with LMWH in cirrhotic patients, this multicenter randomized controlled study attempts to demonstrate the effect of long term LMWH therapy after TIPS on survival in cirrhotic patients with variceal bleeding.
- Conditions
- Liver Cirrhosis
- Being tested
- Rivaroxaban
- Keywords
- liver cirrhosis, Transjugular Intrahepatic Portosystemic Stent Shunt, Anticoagulation, Survival, Additional decompensation
- Medical subject headings
- Liver Cirrhosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
RivaroxabanDrug
Also called Nadroparin or Enoxaparin
10mg/day, for 2 years
| Study group | Role | What they receive |
|---|---|---|
| Anticoagulation | Experimental | Rivaroxaban：10mg/d for 2 years Receives: Drug: Rivaroxaban |
| Non-anticoagulated | No intervention | No anticoagulants will be used. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Transplant-free survival
Measured: 2 years
Secondary outcomes (10)
Number of participants with all-cause rebleeding
Measured: 2 years
Number of participants with overt hepatic encephalopathy
Measured: 2 years
Number of participants with recurrent or worsening ascites
Perform two or more evacuative paracentesis in the following six months
Measured: 2 years
Number of participants with shunt dysfunction
Measured: 2 years
Effect of anticoagulation on liver function estimated by the Child-Pugh and the model for end-stage liver disease scores
Measured: 2 years
Echocardiography findings
Measured: 2 years
Serum levels of bacterial translocation biomarkers and proinflammatory cytokines
Measured: 2 years
Security of anticoagulation in patients with liver cirrhosis
Number of adverse events and adverse reactions in each arm of study. History and clinical evaluation of bleeding and monitoring of hematocrit.
Measured: 2 years
Compliance
Record of unused packaging and information about compliance in a patient diary
Measured: 2 years
Score of Health Related Quality of Life questionnaire，for example, SF-36
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted29 Dec 2016 (estimated)
- Study start14 Jun 2017
- Primary completion31 Dec 2023 (estimated)
- Study completion31 Dec 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Liver CirrhosisStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 254 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Air Force Military Medical University, China
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Guohong Han, Xi'an International Medical Center Hospital
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03005444
- Sponsor's protocol ID
- APPROACH
- Status last verified
- Oct 2022
- First submitted
- 21 Dec 2016
- Last updated
- 25 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
Study at a glance
From the registry record, last updated by the sponsor on 25 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Anticoagulation for Development of Further Decompensation and Survival in Advanced Cirrhosis After Transjugular Intrahepatic Portosystemic Shunt: a Multicenter Randomized Controlled Study
- ClinicalTrials.gov ID
- NCT03005444
- Acronym / sponsor ID
- APPROACH
- Conditions
- Liver Cirrhosis
- Keywords
- liver cirrhosis, Transjugular Intrahepatic Portosystemic Stent Shunt, Anticoagulation, Survival, Additional decompensation
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 254 participants (estimated)
- Lead sponsor
- Air Force Military Medical University, ChinaUniversity, hospital or other
- Study start
- 14 Jun 2017 (actual)
- Primary completion
- 31 Dec 2023 (estimated)
- Study completion
- 31 Dec 2024 (estimated)
- First posted
- 29 Dec 2016 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Recent studies demonstrated that liver cirrhosis was associated with a hypercoagulability state. Besides, bacterial translocation plays an important role in the pathogenesis and complications in patients with decompensated cirrhosis, including infections as well as hepatic encephalopathy and hepatorenal syndrome.
A recent prospective study in a group of 70 patients with liver cirrhosis (Child B and C stages up to 10 points) who were randomized to receive enoxaparin for a year (n = 34) vs no intervention (n = 36) showed that anticoagulant treatment with enoxaparin is safe and effective, significantly reducing risk of PVT development and liver decompensation, markedly improving overall survival. This study provides exciting preliminary data regarding the potential use of prophylactic anticoagulation in improving clinical outcomes in cirrhosis, beyond the prevention of portal vein thrombosis. This study suggested that the effect was partly due to a direct effect of reducing BT and levels of proinflammatory cytokines. However, this study included few patients, was not double blind, and did not have a placebo group. Therefore, despite the spectacular results, the use of prophylactic anticoagulant therapy has not become routine practice in patients with cirrhosis and more studies are needed to assess the potential usefulness of anticoagulation in improving the prognosis of liver cirrhosis.
Transjugular intrahepatic portosystemic shunts (TIPS) are now routinely used to treat the complications of portal hypertension, such as variceal bleeding and refractory ascites. TIPS is the most effective method to prevent rebleeding, however, it is burdened with increased risk of hepatic encephalopathy and deterioration of liver function in patients with advanced cirrhosis. Notably, TIPS can not only relieve portal pressure but also can redirect the portal blood flow through the shunt directly into the systemic circulation which can cause systemic hemodynamic changes.
Given the preliminary data suggesting a beneficial effect of prophylactic anticoagulation with LMWH in cirrhotic patients, this multicenter randomized controlled study attempts to demonstrate the effect of long term LMWH therapy after TIPS on survival in cirrhotic patients with variceal bleeding.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Anticoagulation | Experimental | Drug: RivaroxabanRivaroxaban：10mg/d for 2 years |
| Non-anticoagulated | No intervention | –No anticoagulants will be used. |
Who may qualify
- Ages
- 18 to 75 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| RivaroxabanAlso: Nadroparin or Enoxaparin10mg/day, for 2 years | Drug | Anticoagulation |
Primary outcome
Transplant-free survival
Time frame: 2 years
10 secondary outcomes
Number of participants with all-cause rebleeding
Time frame: 2 years
Number of participants with overt hepatic encephalopathy
Time frame: 2 years
Number of participants with recurrent or worsening ascites
Time frame: 2 years
Number of participants with shunt dysfunction
Time frame: 2 years
Effect of anticoagulation on liver function estimated by the Child-Pugh and the model for end-stage liver disease scores
Time frame: 2 years
Echocardiography findings
Time frame: 2 years
Serum levels of bacterial translocation biomarkers and proinflammatory cytokines
Time frame: 2 years
Security of anticoagulation in patients with liver cirrhosis
Time frame: 2 years
Compliance
Time frame: 2 years
Score of Health Related Quality of Life questionnaire，for example, SF-36
Time frame: 2 years
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 25 Oct 2022.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
11 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing Rivaroxaban in people with Liver Cirrhosis, run by Air Force Military Medical University, China at 11 sites in China.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 25 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 11 sites in China. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Guohong Han, MD,Ph.D (+86-13991969930, 13991969930@126.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Transplant-free survival (time frame: 2 years). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 25 Oct 2022.