Liver Cirrhosis, Portal Vein Thrombosis
Conditions
Keywords
Portal vein thrombosis, Nadroparin calcium, Warfarin, Anticoagulation
Brief summary
The study is aimed at evaluating the efficacy and safety of anticoagulant therapy with nadroparin calcium and warfarin in patients with portal vein thrombosis (PVT).
Detailed description
Portal vein thrombosis (PVT) is a frequent complication of liver cirrhosis, referred to partial or complete thrombosis formed in the lumen of portal vein or/and branches of it. Currently, clinical guidelines of PVT in cirrhotic patients has not been addressed, and anticoagulant therapy of PVT patients with cirrhosis remains controversial. Although numerable studies have reported that anticoagulation therapy is effective, while a majority of them were respective and a few took control into consideration. In addition, no agreement has reached about the safety of anticoagulation. So, the efficacy and safety of anticoagulant therapy needs more prospective randomized controlled trial to be investigated.
Interventions
DRUGNadroparin calcium, warfarin
Nadroparin calcium subcutaneously every 12hs for 1 months followed by warfarin orally for 5 months. INR(international normalized ratio ) was detected every 3-4 days and adjusted carefully by 0.75mg dosage until achieve the target level of 2-3.
Sponsors
Qilu Hospital of Shandong University
Study design
Allocation
RANDOMIZED
Intervention model
PARALLEL
Primary purpose
TREATMENT
Masking
SINGLE (Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Age
18 Years to 75 Years
Healthy volunteers
No
Inclusion criteria
* Age between 18 and 75 years * Liver cirrhosis diagnosis based on clinical, laboratory, and imaging studies, and PVT diagnosed by abdominal contrast-enhanced computed tomography, contrast-enhanced MRI, or portal angiography
Exclusion criteria
* Cavernous transformation of the portal vein * Uncontrolled active bleeding * Platelet count lower than 10\*10\^9/L * Creatinine more than 170 mmol/L * Ongoing or received antithrombotic/thrombolytic treatment * Primary thrombophilia * Budd-Chiari syndrome * Pregnancy or breast-feeding period * Severe cardiopulmonary diseases * Severe systemic infection or sepsis * Inability to sign informed consent
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Recanalization Rate | 6 months | For each venous segment, the vein and residual patent lumen were outlined at the level of the maximum thrombosis. Total lumen area and patent lumen area were calculated with commercially available software. The degree of thrombus occlusion was estimated as a percentage by thrombosis area/total lumen area×100%. The primary outcome was the overall recanalization rate, both complete and partial. Complete recanalization was referred to the complete disappearance of the thrombus in the portal vein trunk, at least one of the two intrahepatic portal vein branches, SMV and SV. Partial recanalization was defined as a more than 50% reduction of the thrombus, with the thrombus not extending to other veins. |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| Rate of Bleeding | 6 months | Risk of bleeding episodes |
Countries
China
Participant flow
Participants by arm
| Arm | Count |
|---|---|
| Nadroparin Calcium-warfarin Sequential (NWS) Therapy Group Nadroparin calcium every 12 hours for 1 month followed by an oral administration of warfarin for 5 months.
Nadroparin calciumsubcutaneously every 12hs for 1 months followed by warfarin orally for 5 months. INR(international normalized ratio ) was detected every 3-4 days and adjusted carefully by 0.75mg dosage until achieve the target level of 2-3. | 32 |
| Control Group No anticoagulation therapy. | 32 |
| Total | 64 |
Baseline characteristics
| Characteristic | Nadroparin Calcium-warfarin Sequential (NWS) Therapy Group | Control Group | Total |
|---|---|---|---|
| Age, Continuous | 55 year STANDARD_DEVIATION 9 | 53 year STANDARD_DEVIATION 10 | 54 year STANDARD_DEVIATION 9 |
| Albumin (g/L) | 36.14 g/L STANDARD_DEVIATION 5.25 | 35.03 g/L STANDARD_DEVIATION 4.45 | 35.64 g/L STANDARD_DEVIATION 4.89 |
| Ascites No | 15 Participants | 12 Participants | 27 Participants |
| Ascites Yes | 17 Participants | 20 Participants | 37 Participants |
| Child-Pugh score | 6.51 units on a scale STANDARD_DEVIATION 1.27 | 6.81 units on a scale STANDARD_DEVIATION 1.44 | 6.59 units on a scale STANDARD_DEVIATION 1.35 |
| Cholesterol (mmol/L) | 3.47 mmol/L STANDARD_DEVIATION 1.02 | 3.50 mmol/L STANDARD_DEVIATION 1.1 | 3.48 mmol/L STANDARD_DEVIATION 1.05 |
| Creatinine (μmol/L) | 60.90 μmol/L STANDARD_DEVIATION 16 | 65.78 μmol/L STANDARD_DEVIATION 16.07 | 63.2 μmol/L STANDARD_DEVIATION 16.1 |
| D-dimer(μg/mL) | 1.14 μg/mL STANDARD_DEVIATION 1.05 | 1.50 μg/mL STANDARD_DEVIATION 1.32 | 1.31 μg/mL STANDARD_DEVIATION 1.19 |
| Endoscopic treatment No | 19 Participants | 23 Participants | 42 Participants |
| Endoscopic treatment Yes | 13 Participants | 9 Participants | 22 Participants |
| Esophageal varices No | 6 Participants | 5 Participants | 11 Participants |
| Esophageal varices Yes | 26 Participants | 27 Participants | 53 Participants |
| Etiology Alcoholic | 5 Participants | 3 Participants | 8 Participants |
| Etiology Cryptogenic | 4 Participants | 5 Participants | 9 Participants |
| Etiology Hepatitis B virus (HBV) | 23 Participants | 23 Participants | 46 Participants |
| Etiology Hepatitis C virus (HCV) | 0 Participants | 1 Participants | 1 Participants |
| Extent of portal vein thrombosis(PVT) Main portal vein(MPV) only | 12 Participants | 14 Participants | 26 Participants |
| Extent of portal vein thrombosis(PVT) MPV + SMV | 17 Participants | 9 Participants | 26 Participants |
| Extent of portal vein thrombosis(PVT) MPV + SMV + SV | 1 Participants | 2 Participants | 3 Participants |
| Extent of portal vein thrombosis(PVT) MPV + SV | 0 Participants | 2 Participants | 2 Participants |
| Extent of portal vein thrombosis(PVT) Splenic vein(SV) only | 0 Participants | 2 Participants | 2 Participants |
| Extent of portal vein thrombosis(PVT) Superior mesenteric vein(SMV) only | 2 Participants | 3 Participants | 5 Participants |
| International normalized ratio (INR) | 1.34 ratio STANDARD_DEVIATION 0.23 | 1.36 ratio STANDARD_DEVIATION 0.2 | 1.35 ratio STANDARD_DEVIATION 0.21 |
| Low-density lipoprotein cholesterol(LDL-C,mmol/L) | 1.91 mmol/L STANDARD_DEVIATION 0.69 | 1.77 mmol/L STANDARD_DEVIATION 0.68 | 1.85 mmol/L STANDARD_DEVIATION 0.68 |
| Model for end-stage liver disease (MELD) score | 9.13 units on a scale STANDARD_DEVIATION 3.39 | 10.00 units on a scale STANDARD_DEVIATION 3.65 | 9.51 units on a scale STANDARD_DEVIATION 3.5 |
| Platelet (*10^9 cells/L) | 126.22 *10^9 cells/L STANDARD_DEVIATION 170.86 | 134.63 *10^9 cells/L STANDARD_DEVIATION 137.48 | 130 *10^9 cells/L STANDARD_DEVIATION 150 |
| Race and Ethnicity Not Collected | — | — | 0 Participants |
| Sex: Female, Male Female | 11 Participants | 11 Participants | 22 Participants |
| Sex: Female, Male Male | 21 Participants | 21 Participants | 42 Participants |
| Splenectomy/Partial splenic embolization(PSE) No | 23 Participants | 19 Participants | 42 Participants |
| Splenectomy/Partial splenic embolization(PSE) Yes | 9 Participants | 13 Participants | 22 Participants |
| Total bilirubin (μmol/L) | 18.64 μmol/L STANDARD_DEVIATION 9.76 | 22.31 μmol/L STANDARD_DEVIATION 17 | 20.3 μmol/L STANDARD_DEVIATION 13.6 |
| Triglyceride (mmol/L) | 0.95 mmol/L STANDARD_DEVIATION 0.51 | 0.83 mmol/L STANDARD_DEVIATION 0.36 | 0.89 mmol/L STANDARD_DEVIATION 0.44 |
Adverse events
| Event type | EG000 affected / at risk | EG001 affected / at risk |
|---|---|---|
| deaths Total, all-cause mortality | 0 / 32 | 0 / 32 |
| other Total, other adverse events | 1 / 32 | 0 / 32 |
| serious Total, serious adverse events | 0 / 32 | 0 / 32 |
Outcome results
Primary
Recanalization Rate
For each venous segment, the vein and residual patent lumen were outlined at the level of the maximum thrombosis. Total lumen area and patent lumen area were calculated with commercially available software. The degree of thrombus occlusion was estimated as a percentage by thrombosis area/total lumen area×100%. The primary outcome was the overall recanalization rate, both complete and partial. Complete recanalization was referred to the complete disappearance of the thrombus in the portal vein trunk, at least one of the two intrahepatic portal vein branches, SMV and SV. Partial recanalization was defined as a more than 50% reduction of the thrombus, with the thrombus not extending to other veins.
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nadroparin Calcium-warfarin Sequential Therapy Group | Recanalization Rate | 20 Participants |
| Control Group | Recanalization Rate | 11 Participants |
Secondary
Rate of Bleeding
Risk of bleeding episodes
Time frame: 6 months
| Arm | Measure | Value (COUNT_OF_PARTICIPANTS) |
|---|---|---|
| Nadroparin Calcium-warfarin Sequential Therapy Group | Rate of Bleeding | 1 Participants |
| Control Group | Rate of Bleeding | 0 Participants |