Background: In Cambodia, hepatitis C constitutes a significant public health challenge, particularly among older adults (>45 years) for whom prevalence is estimated to be 5%. To facilitate the elimination of hepatitis C among the general population, enhancing access to screening and treatment is imperative. In this regard, the evaluation of community-based screening programs emerges as a crucial step toward improving health care accessibility.

Objective: This study aims to assess the comparative efficacy of a community-based versus a facility-based approach in enhancing the uptake of hepatitis C antibody testing among the general population older than 40 years of age in Cambodia.

Methods: The CAM-C (Community Versus Facility-Based Services to Improve the Screening of Active Hepatitis C Virus Infection in Cambodia) study uses a cluster-randomized controlled trial design across two Cambodian provinces to compare community-based and facility-based hepatitis testing interventions. Sampling involves a multistage cluster approach, targeting individuals older than 40 years of age due to their higher prevalence and risk of chronic hepatitis complications. This study incorporates a qualitative analysis of acceptability and a cost-effectiveness comparison. Interventions include facility-based testing with subsequent referral and community-based testing with direct in-home assessments. Follow-up for positive cases involves comprehensive management and potential direct-acting antiviral treatment. This study aims to identify a significant increase in testing uptake, requiring the screening of 6000 individuals older than 40 years of age, facilitated by a structured sampling and intervention approach to minimize contamination risks.

Results: The final protocol including the quantitative, qualitative, and cost-effectiveness part of the study was registered and was approved in 2019 by the National Ethical Cambodian for Health Research. Inclusions were completed by mid-2024, with analyses starting in May 2024.

Conclusions: Using a mixed methods approach that combines a robust methodology (cluster-randomized controlled trial) with a cost-effectiveness analysis and qualitative research, such a study should provide invaluable information to guide the Ministry of Health in its hepatitis C virus screening strategy and move toward elimination.

Trial registration: ClinicalTrials.gov NCT03992313; https://clinicaltrials.gov/study/NCT03992313.

International registered report identifier (irrid): DERR1-10.2196/63376.