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PROLIFICA - West African Treatment Cohort for Hepatitis B (WATCH)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT02129829
Recruitment Status : Completed
First Posted : May 2, 2014
Last Update Posted : September 28, 2020
Sponsor:
Collaborators:
Medical Research Council Unit, The Gambia
Department of State for Health and Social Welfare, The Gambia
UFR Sante de Thies, Senegal
Cheikh Anta Diop University, Senegal
Institut National de la Santé Et de la Recherche Médicale, France
International Agency for Research on Cancer
Information provided by (Responsible Party):
Imperial College London

Tracking Information
First Submitted Date April 30, 2014
First Posted Date May 2, 2014
Last Update Posted Date September 28, 2020
Actual Study Start Date October 2011
Actual Primary Completion Date July 31, 2018   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures
 (submitted: June 1, 2015)
Incidence of HCC or decompensated cirrhosis [ Time Frame: 5 years ]
Subjects will be reviewed 6 monthly with liver biochemistry and ultrasound to detect onset of hepatocellular carcinoma or decompensated cirrhosis
Original Primary Outcome Measures
 (submitted: April 30, 2014)
Incidence of HCC or decompensated cirrhosis [ Time Frame: 5 years ]
Subjects will be reviewed 6 monthly with liver biochemistry and ultrasound to detect onset of hepatocellular carcinoma or decompnsated cirrhosis
Change History
Current Secondary Outcome Measures
 (submitted: April 30, 2014)
  • Uptake of screening [ Time Frame: 2 years ]
    Proportion of community subjects who accept screening tests
  • Prevalence of HBV infection [ Time Frame: 2 years ]
    Proportion of patients who test positive for HBsAg
  • Rate of linkage into care [ Time Frame: 2 years ]
    Proportion of patients who test positive for HBsAg who attend clinic for assessment
  • Treatment rate [ Time Frame: 2 years ]
    Proportion of patients with HBsAg who meet EASL treatment criteria
Original Secondary Outcome Measures Same as current
Current Other Pre-specified Outcome Measures
 (submitted: June 1, 2015)
  • Reliability of PoC test [ Time Frame: 2 years ]
    Sensitivity and specificity of capillary blood sample HBsAg test applied at point of care
  • Accuracy of non-invasive fibrosis assessment [ Time Frame: 2 years ]
    Sensitivity, specificity and ROC analysis of Fibroscan, APRI and FIB4 tests compared to liver biopsy to assess liver fibrosis
Original Other Pre-specified Outcome Measures
 (submitted: April 30, 2014)
  • Relaibility of PoC test [ Time Frame: 2 years ]
    Sensitivity and specificity of capillary blood sample HBsAg test applied at point of care
  • Accuracy of non-invasive fibrosis assessment [ Time Frame: 2 years ]
    Sensitivity, specificity and ROC analysis of Fibroscan, APRI and FIB4 tests compared to liver biopsy to assess liver fibrosis
 
Descriptive Information
Brief Title PROLIFICA - West African Treatment Cohort for Hepatitis B
Official Title Prevention of Liver Fibrosis and Cancer in Africa. Observational Study of Screening, Assessment and Treatment for Chronic Hepatitis B Virus Infection
Brief Summary The West African Treatment Cohort for Hepatitis B (WATCH) study is a component of the European Commission Funded FP7 project PROLIFICA. It aims to evaluate a number of steps required to successfully treat patients with chronic hepatitis B virus infection to prevent cirrhosis and liver cancer. The first step is to determine whether screening for hepatitis B using a point of care test is feasible and effective. The second is to monitor linkage from screening into care. The third is to evaluate cheap non-invasive assessments to determine the need for treatment. The fourth is to determine what proportion of patients meet treatment eligibility criteria. The fifth step is to establish a treatment cohort which can be used to measure adherence to therapy and avoidance of HBV related complications. A parallel untreated cohort will be established to determine whether treatment criteria are relevant in this West African setting by monitoring for complications of HBV infection.
Detailed Description

Objectives Primary:

To determine whether suppression of HBV with a nucleotide analogue reduces the risk of liver cancer in West African populations.

Secondary:

To demonstrate that HBV replication can be effectively suppressed with a nucleotide analogue in West African populations To evaluate whether European treatment guidelines are applicable in West Africa To establish the applicability and efficacy of population based screening, clinical assessment and treatment in West Africa To enumerate the proportion of the adult population who carry HBV To evaluate the proportion of the HBV infected population who meet European Association for Study of the Liver (EASL) criteria for treatment

Endpoints Primary:

Incidence of Hepatocellular Carcinoma over the period of study in a treated cohort of patients with chronic HBV compared to historical controls

Secondary:

Proportion of adult population in Gambia and Senegal with chronic HBV infection Proportion of patients with chronic HBV infection who meet EASL treatment criteria Proportion of patients with undetectable HBV DNA < 400 copies/ml at 1, 2, 3, 4 and 5 years of treatment.

Incidence of hepatocellular Carcinoma in patients who do not meet EASL treatment criteria.

Treatment adherence rate. Average change in Fibroscan score after 3 and 5 years of treatment Emergence of resistance to treatment

Study Phase 4

Study Design A two part study:

Part 1 - Population based screening for HBV infection using a point-of-care test.

Part 2 - Non-randomised, open label, treatment cohort with parallel observation cohort

Number of Subjects Part 1:

Approximately 13,500 adults from the general population.

Part 2:

300 subjects in the treatment group 600 subjects in the observation group

Study Population Part 1:

Males and females aged over 30 years

Part 2:

Patients with chronic hepatitis B virus infection identified through population based screening.

Treatment Cohort There will be a single treatment group of 300 patients who meet EASL treatment criteria.

Schedule of Study Visits Part 1:

A single visit to an individual at their home or workplace when screening for HBV infection will be performed using a point-of-care test..

Part 2:

One screening visit will be performed to determine viral load, liver function tests, clinical examination, ultrasound examination and liver fibrosis assessment.

A second visit, 1 - 3 months later, will be used to verify viral load and ALT values

For those on treatment cohort:

A baseline visit will take place 2 weeks after the second screening visit and study drug will be dispensed with instructions for the patient.

First follow-up will be at 1 month to check adherence Second follow-up will be at 3 months for viral load and liver functions tests Treatment subjects will be seen every 3 months to dispense study drug and check compliance Viral load, liver function, renal function, AFP and ultrasound will be performed every 6 months.

Serum/plasma and urine samples for biomarkers of cancer development will be taken at baseline and annually.

Population Screening (Part 1 only) Communities will be sensitised about the study prior to visits by fieldworkers to individual homes, places of work or recreational facilities. A point-of-care test based on the detection of hepatitis B surface antigen (HBsAg) in a finger-prick blood sample will be used for screening. Subjects with a positive test will be given a hospital appointment for full clinical assessment.

Efficacy Evaluations (Part 2 only) Detection of liver cancer - Surveillance for liver cancer will be made using ultrasound and serum AFP every 6 months on all subjects. In some centres further imaging will be available.

Liver cancer will be diagnosed according to the following criteria:

  • Liver mass with typical features of hepatocellular carcinoma on two imaging modalities (ultrasound, bubble ultrasound or CT), or
  • liver mass on ultrasound and AFP > 400 iu/ml or
  • histological or cytological confirmation of diagnosis.

Viral Load - viral load will be measure on EDTA plasma samples using an in-house real-time PCR assay verified for accuracy against commercial assays every 6 months.

Safety Evaluations (Part 2 only) Liver function tests, serum phosphate and renal function will be tested every 6 months

Evaluation of treatment guidelines Subjects who do not meet the EASL treatment criteria at baseline will be enrolled in the observational study with surveillance for liver cancer every 6 months

Detection of viral resistance Viral load monitoring of patients in the treatment study every 6 months will be used to detect possible virological resistance. A rise in viral load from nadir values or reappearance of detectable viraemia in patients who had achieved undetectable viral load will be investigated for emergence of viral sequence variants and for adherence to therapy

Study Type Observational
Study Design Observational Model: Cohort
Time Perspective: Prospective
Target Follow-Up Duration Not Provided
Biospecimen Retention:   Samples With DNA
Description:
Serum, plasma, urine and DNA
Sampling Method Probability Sample
Study Population All adults are included for community screening. Selection criteria (below) are applied for recruitment into cohorts
Condition
  • Hepatitis B, Chronic
  • Hepatocellular Carcinoma
Intervention Drug: Tenofovir disoproxil
Tenofovir disoproxil 245 mg once daily
Other Name: Viread
Study Groups/Cohorts
  • Observational Group
    Patients whose viral load, ALT value and fibrosis status does not meet EASL criteria for treatment and are observed 6 monthly
  • Treatment Group (Tenofovir disoproxil)
    Patients who meet EASL treatment criteria who receive Tenofovir disoproxil
    Intervention: Drug: Tenofovir disoproxil
Publications *

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status Completed
Actual Enrollment
 (submitted: June 14, 2019)
1079
Original Estimated Enrollment
 (submitted: April 30, 2014)
1000
Actual Study Completion Date July 31, 2018
Actual Primary Completion Date July 31, 2018   (Final data collection date for primary outcome measure)
Eligibility Criteria

Inclusion Criteria:

  • Adult Informed consent HBsAg positive Resident in Gambia or Senegal

Exclusion Criteria:

  • HIV infection HCV infection Known liver cancer
Sex/Gender
Sexes Eligible for Study: All
Ages 18 Years and older   (Adult, Older Adult)
Accepts Healthy Volunteers No
Contacts Contact information is only displayed when the study is recruiting subjects
Listed Location Countries Gambia,   Senegal
Removed Location Countries  
 
Administrative Information
NCT Number NCT02129829
Other Study ID Numbers WMDH-P34114
Has Data Monitoring Committee No
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement
Plan to Share IPD: No
Responsible Party Imperial College London
Study Sponsor Imperial College London
Collaborators
  • Medical Research Council Unit, The Gambia
  • Department of State for Health and Social Welfare, The Gambia
  • UFR Sante de Thies, Senegal
  • Cheikh Anta Diop University, Senegal
  • Institut National de la Santé Et de la Recherche Médicale, France
  • International Agency for Research on Cancer
Investigators
Principal Investigator: Mark Thursz, MD FRCP Imperial College London
PRS Account Imperial College London
Verification Date September 2020