- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT04032860
RCT of Different Effects of Nucleot(s)Ide Analogues on the Prognosis of HBV-HCC Patients After Curative Resection
The Different Effects of Nucleotide and Nucleoside Analogues on the Prognosis of Hepatitis B Virus-Related Hepatocellular Carcinoma Patients After Curative Resection:a Randomized Controlled Trial
Study Overview
Status
Conditions
Intervention / Treatment
Detailed Description
The study was designed to compare the efficacy of ETV and TDF for patients with HBV-related HCC patients undergoing curative liver resection. Eligible patients were randomly assigned in a 1:1 ratio via computer-generated allocation to either the ETV group or TDF group. A block size and strata were used in the randomization. In 2015, the American Association for the Study of Liver (AASLD) adopted ETV and TDF as first-line antiviral treatments for chronic hepatitis B. Patients in the ETV group received ETV tablets (RunZhong, CHIATAI TIANQING, China) 0.5 mg/d orally starting from 2-4 weeks before surgery; those in the TDF group receive TDF tablets(Viread, Aspen Port Elizabeth, China) 300 mg/d orally starting from 2-4 weeks before surgery. Antiviral treatment was continued unless there was unacceptable toxicity or withdrawal of consent.
Preoperatively, all patients underwent chest radiography and at least 2 dynamic imaging examinations (contrast-enhanced ultrasound, contrast-enhanced computed tomography(CT) or magnetic resonance imaging(MRI)). HBsAg and hepatitis B e antigen (HBeAg), HBV-DNA load, anti-HCV, alpha-fetoprotein (AFP), carcinoembryonic antigen(CEA), carbohydrate antigen 19-9(CA19-9), liver function and HBV genotypes were serologically examined within 1 week before surgery. Additional serum samples were collected to test single-nucleotide polymorphisms(SNPs) of the interleukin 28B(IL-28B) gene and serum levels of interferon(IFN)-λ1, IFN-λ2, IFN-λ3, IL-1β, tumor necrosis factor alpha(TNF-α), IL-6, IL-8 and IL-10. All serum and DNA samples were stored at -80°C until use.
After general anesthesia, surgery was performed as the standard protocol. Intraoperative ultrasonography was performed to assess the relationship of the tumor to vascular structures and to eliminate the extrahepatic metastasis. Pringle's maneuver was applied to occlude the blood inflow of the liver with cycles of 15 minutes clamp time and 5 minutes unclamped time. Liver resection was carried out by the Cusa Excel Ultrasonic Surgical Aspirator System(CUSA).
In the study, the primary outcome measures included both recurrence and overall survival rates from the date of the operation. Secondary outcome measures included patient tolerance of antiviral treatment, virologic response, liver function and additional cytokines such as IFN-λ1 IFN-λ2, IFN-λ3, IL-1β, TNF-α, IL-6, IL-8 and IL-10. All the patients received follow-up monitoring 1 month after the operation, every 3 months thereafter during the first 3 years, and then every 6 months in subsequent years. Physical examination, blood cell and differential counts, renal and liver function tests, AFP levels, HBV serology and HBV-DNA levels, serum IFN-λ level and imaging examinations were included in the follow-up examinations when necessary. Follow-up was continued until August 2020 when all surviving patients had a minimum follow-up of 24 months.
Tumor recurrence was diagnosed based on the identification of a new lesion on at least 2 radiological examinations and increased AFP levels (>100 ng/mL). Patients with tumor recurrence were actively treated with salvage liver transplantation, repeat hepatic resection, radiofrequency ablation, transcatheter arterial chemoembolization(TACE), sorafenib, and/or chemotherapy, depending on the extent of the disease, the liver function, and general condition of the patient.
Study Type
Enrollment (Actual)
Phase
- Phase 4
Contacts and Locations
Study Locations
-
-
Sichuan
-
Chengdu, Sichuan, China, 610000
- West China Hospital, Sichuan University
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- older than 18 years and less than 69 years old;
- HBsAg positive HCV antibody negative and HIV antibody negative;
- HBV-DNA>200 IU/mL;
- BCLC(Barcelona Clinic Liver Cancer) staging O and A stage;
- Platelet100×10^9/L;
- Liver function Child-Pugh A,with no invasion in portal vein, hepatic vein and two large branches, no extrahepatic metastasis;
- Creatinine clearance rate≥ 70 mL/min;
- Antiviral treatment was not performed before surgery or antiviral treatment was accepted in a short term (<3 months);
- No treatment was performed before the operation. The results of postoperatively histopathological biopsy were HCC;
- The patients agree to participate in the clinical trial.
Exclusion Criteria:
- The image found extrahepatic lymph nodes or visceral metastasis, the existence of large vascular invasion, the existence of bile duct embolus in the first operation;
- The patient combined with a malignant tumor of other organs or had a history of other malignant tumors in other organs;
- Liver function decompensation, such as: upper gastrointestinal bleeding, refractory ascites, coagulation dysfunction and so on;
- contraindications to surgery;
- Patients with poor compliance and not adhered to the follow-ups;
- Patients refused to participate in the clinical trial.
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: ETV group
group in which patients take ETV as antiviral therapy after curative treatment
|
patients with HBV-HCC would take ETV as antiviral therapy before curative treatment to see the prognosis after surgery
Other Names:
|
Experimental: TDF group
group in which patients take TDF as antiviral therapy after curative treatment
|
patients with HBV-HCC would take TDF as antiviral therapy before curative treatment to see the prognosis after surgery
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Overall survival
Time Frame: 1,3,5 years
|
the difference of overall survival between two groups
|
1,3,5 years
|
Recurrence-free survival
Time Frame: 1,3,5 years
|
the difference of overall survival between two groups
|
1,3,5 years
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
cytokines
Time Frame: 1-3 years
|
several cytokines secreted by patients after antiviral therapy such as interferon λ3
|
1-3 years
|
Viral reactivity
Time Frame: 1,3 year
|
HBsAg,HBsAb,HBeAg,HBeAb,HBcAb
|
1,3 year
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: He Linye, Doctor, WestChina Hospital
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Anticipated)
Study Completion (Anticipated)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- 1185022016
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
IPD Plan Description
IPD Sharing Time Frame
IPD Sharing Access Criteria
IPD Sharing Supporting Information Type
- Study Protocol
- Informed Consent Form (ICF)
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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