Study on the Optimal Strategy for Acute-on-chronic Liver Failure Combined With Traditional Chinese and Modern Medicine: a Multi-center, Randomized and Controlled Study
Trial Snapshot
- Phase
- Not Applicable
- Status
- Completed
- Sponsor
- Enrollment
- 516
- Locations
- 15
- Primary Endpoint
- transplant free survival
Study Overview
Brief Summary
Background: Acute-on-chronic liver failure (ACLF) is a syndrome characterized by acute deterioration in the setting of chronic liver disease associated with high short-term mortality. Currently, there is no specific treatment for patients with ACLF. Our previous results showed that Chinese herbal medicine (CHM) could reduce the mortality rate and the incidence of complications of ACLF effectively. In this study, we aim to conduct the multi-center randomized controlled trial to evaluate the effect of unified CHM formulas and provide propagable and high-level evidence for clinical practice.
Methods/design: This is a prospective, multicenter, centrally randomized controlled trial. Five hundred and ten patients diagnosed with HBV-related ACLF will be allocated in a 1:1 ratio to SMT group (standard medical therapy) and CHM group (CHM and SMT). The primary outcome is the transplant-free mortality rates at week 4, 8, 12, 24 and 48. Secondary outcomes include (1) the incidence of adverse reactions, (2) influence on liver function, (3) the incidence of serious complications and (4) the level of inflammatory cytokines.
Discussion: The effectiveness and safety of CHM formulas are assessed in the treatment of ACLF.
Detailed Description
Study design This prospective, multi-center, parallel, centrally randomized controlled trial was designed in accordance with the Consolidated Standards of Reporting Trials (CONSORT) and Standard Protocol Items: Recommendations for Interventional Trials (SPIRIT) guidelines, which is led by the principal investigator from 302 military hospital in Beijing, will be carried out from September 2018 and December 2020 among 16 tertiary academic hospitals in China. Patients with hepatitis B virus (HBV) related acute-on-chronic liver failure (ACLF) will be randomly allocated to the CHM group or the SMT group in a 1:1 ratio. The last patient will be enrolled before August 2019 to make sure the availability of 48 week's survival status by the end of this study. We will decide whether to expand additional institutions to guarantee adequate enrolments after interim assessment of effective participant numbers around December 2018. Patients in the SMT group will receive the standard medical treatment, and patients in the CHM group will receive rhubarb decoction enema for 1 week and CHM for 8 weeks additionally. All patients will be followed at pre-designed time points after 8 weeks' observational period until August 30, 2020 for the primary outcome and secondary outcomes.
The study is consistent with Good Clinical Practice (GCP) guidelines and has been approved by 302 military hospital ethics review committee(2018007D). Written informed consent is requisite to be signed by the patients or the authorized person under the willingness. The privacy and data of all participants will be protected carefully before, during and after the trial.
Patients will be consented and enrolled by co-principal investigators at each institution and managed by care providers including residents, attending physicians and nurses according to the protocol. Most of the patients will be treated in hospital for 8 weeks so clinicians can supervise the administration of CHM, in addition, the policy of reimbursement filed by the lab results at determined time points will boost the regular follow-up of this study.
Diagnostic criteria The diagnosis of HBV-ACLF refers to the guideline of liver failure issued by Chinese Group on the Study of Severe Hepatitis B (COSSH) in 2012.
The traditional Chinese medicine (TCM) syndrome was judged by two qualified senior TCM physicians simultaneously based on the published criteria to decide what CHM will be given, and the discrepancy will be solved by consulting another senior physician.
Study Design
- Study Type
- Interventional
- Allocation
- Randomized
- Intervention Model
- Parallel
- Primary Purpose
- Treatment
- Masking
- Single (Outcomes Assessor)
Eligibility Criteria
- Ages
- 16 Years to 65 Years (Child, Adult, Older Adult)
- Sex
- All
- Accepts Healthy Volunteers
- Yes
Inclusion Criteria
- •In-patients with acute-on-chronic liver failure;
- •Patients with chronic hepatitis B or compensatory cirrhosis of hepatitis B;
- •Patients who is willing to sign the informed consent;
- •Patients aged among 16~65 years old.
Exclusion Criteria
- •Acute liver failure, or sub acute liver failure, or chronic liver failure;
- •Acute-on-chronic liver failure not caused by hepatitis B but other disease such as autoimmune, drug, alcohol, toxic, parasites;
- •Pregnant or lactating women;
- •Primary liver cancer;
- •Combined with other severe systematic disease and mental disease;
- •Anti-HIV positive or combined with infection of hepatitis A, C, D, E virus or cytomegalovirus, Epstein-Barr virus;
- •Enrolled in other clinical studies in last three months;
- •Person unwilling to cooperate;
- •poor compliance, unable guarantee completing the protocol;
- •Complicated with severe cerebral edema, severe infection, type I liver-kidney symptom, and gastrointestinal hemorrhage.
Arms & Interventions
Chinese herbal medicine
One dosage of Chinese herbal medicine by oral administration per day for 8 weeks. For patients who cannot take oral medicine can be switched to colon route by the colonic therapy system（IMS-100A produced by Sunny Medical in Beijing China).
Intervention: Chinese herbal medicine (Drug)
Chinese herbal medicine
One dosage of Chinese herbal medicine by oral administration per day for 8 weeks. For patients who cannot take oral medicine can be switched to colon route by the colonic therapy system（IMS-100A produced by Sunny Medical in Beijing China).
Intervention: Control (blank) (Other)
Control (blank)
Patients in the control group only receive the standard medical treatment (SMT), no control drug with CHM.
Intervention: Control (blank) (Other)
Outcomes
Primary Outcomes
transplant free survival
Time Frame: week 12
transplant free survival at the time point of week 12
Secondary Outcomes
- liver function assessed by Child-Pugh score(week 12)
- Quality of life assessed by WHOQOL-BRIEF(week 12)
- incidence of complications(from week 1 to week 12)
- liver function assessed by MELD score(week 12)
- transplant free survival(week 24)
Investigators
Man Gong
Professor
Beijing 302 Hospital