Clinical Prognostic Score to Predict Relapse in VL (CPS)

Comprehensive Clinical and Laboratory Assessment of Visceral Leishmaniasis to Develop Clinical Prognostic Tools to Predict Relapse: a Prospective Cohort Study in Ethiopia

This prospective cohort study has the aim to develop a prognostic tool to predict relapse in patients suffering from visceral leishmaniasis (VL) from VL endemic regions in Ethiopia.

Therefore, comprehensive clinical and laboratory characterization of all confirmed VL patients before and during treatment will be performed in order to identify the factors that determine prognosis of the patients. This approach would result in more efficient patient care and would reduce the case fatality and morbidity, and improve follow-up and care for those at risk of VL relapse.

Study Overview

• Status: Recruiting
• Conditions: Visceral Leishmaniasis
• Intervention / Treatment: Other: No intervention

Detailed Description

Certain patient groups seem to be at higher risk of poor outcomes. Although the average case fatality rate was <10% in Ethiopia , certain subgroups of VL patients are at significantly higher risk of dying, with case fatality rates as high as 39% when patients coinfected with HIV or sepsis. The host's immunocompetence appears to play a critical factor associated with disease development, severity, treatment success and disease relapse. Yet, a substantial group of immunocompetent patients also fail to respond well to treatment, or develop relapse after cure. Relapse is increasingly recognized as an important clinical challenge, with 10-15% estimated to develop relapse in the Ethiopian setting. Understanding which factors determine prognosis among VL patients is key in improving outcomes, as high-risk patients can be identified and receive additional monitoring, care, investigations or preferential treatment with safer or more effective drugs.

One of the strategies to improve patient outcome is identification of factors that determine the prognosis of a patient. These factors can be used in clinical decision tools to provide the most appropriate care for each patient. With the key prognostic factors, patients can be stratified in high and low risk of relapse, treatment failure and mortality and can be treated accordingly, providing intensive monitoring and/or treatment of comorbidities of high-risk patients and a more decentralized follow-up for low-risk patients. This approach would result in more efficient patient care and would reduce the case fatality and morbidity, and improve follow-up and care for those at risk of VL relapse.

No clinical tools for prediction of relapse and treatment failure currently exist. The existing clinical tools for predicting mortality developed so far have a fair accuracy but these tools could further be improved by using prognostic markers both before and during treatment and including more relevant parameters which were previously ignored, such as more laboratory parameters including coagulation profile, blood culture, immunological markers and more relevant clinical parameters such as sepsis and comorbidities.

This study will perform a comprehensive clinical and laboratory characterization of all confirmed VL patients before and during treatment with the main objective to develop a prognostic tool for unfavorable outcome among hospitalized patients. It is planned to develop tools of different complexity, geared towards the capacity of the health facility and also study the added effect of each variable in the tool. The data from this study will address a number of outstanding unanswered questions that could help to improve or standardize VL management.

• Study Type: Observational
• Enrollment (Estimated): 741

Contacts and Locations

• Study Contact: Name: Saskia van Henten, MD; Phone Number: +32(0)32476556; Email: svanhenten@itg.be

Study Locations

• Ethiopia
  • Gondar, Ethiopia
    • Recruiting
    • University of Gondar
    • Contact: Eleni Ayele

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 12 years and older (Child, Adult, Older Adult)
• Accepts Healthy Volunteers: No

• Sampling Method: Probability Sample

Study Population

Patients with clinically or parasitologically confirmed VL in Northern Ethiopia

Description

Inclusion Criteria:

• clinically or parasitologically confirmed VL

Exclusion Criteria:

• Age under 12 years
• VL patients already on treatment for 3 days or more
• Severe critical condition or other circumstances that make the study medically inadvisable
• Unlikely to adhere to follow up visits during the study period (e.g. patients who live or work very far away) AND not reachable by phone for follow-up information
• Pregnant or lactating woman

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
VL patients; VL infected individuals residing in/ with travel history to VL-endemic areas in Northern Ethiopia	Other: No intervention; No intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Identification of risk factors for relapse	The association between development of relapse and potential risk factors (demographic/clinical characteristics as well as host immunity/Leishmania infection markers)	December 2026
Prognostic tool for relapse	A clinical decision algorithm, prioritizing and integrating identified risk factors, that is able to most efficiently predict the risk of developing relapse within 12 months after start of treatment	December 2026

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Patterns in host immune markers for VL relapse, treatment failure and death	The association between the risk of VL relapse/ treatment failure/ death and the levels and evolution of the different host immune markers.	December 2026
Identification of risk factors for treatment failure	The association between the occurence of treatment failure and potential risk factors (demographic/clinical characteristics as well as host immunity/Leishmania infection markers)	December 2026
Identification of risk factors for death	The association between occurrence of death and potential risk factors (demographic/clinical characteristics as well as host immunity/Leishmania infection markers)	December 2026

Collaborators and Investigators

• Sponsor: Institute of Tropical Medicine, Belgium
• Collaborators: University of Gondar
• Investigators: Principal Investigator: Eleni Ayele, MD, University of Gondar, Gondar, Ethiopia; Study Chair: Saskia van Henten, MD, Institute of Tropical Medicine Antwerp, Antwerp, Belgium

Study record dates

Study Major Dates

• Study Start (Actual): February 3, 2023
• Primary Completion (Estimated): December 31, 2026
• Study Completion (Estimated): June 30, 2027

Study Registration Dates

• First Submitted: October 27, 2022
• First Submitted That Met QC Criteria: October 27, 2022
• First Posted (Actual): November 2, 2022

Study Record Updates

• Last Update Posted (Estimated): March 5, 2024
• Last Update Submitted That Met QC Criteria: March 4, 2024
• Last Verified: March 1, 2024

More Information

Terms related to this study

• Keywords: relapse; Ethiopia; leishmaniasis; visceral; neglected
• Additional Relevant MeSH Terms: Pathologic Processes; Skin Diseases; Infections; Disease Attributes; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Skin Diseases, Parasitic; Skin Diseases, Infectious; Euglenozoa Infections; Recurrence; Leishmaniasis; Leishmaniasis, Visceral
• Other Study ID Numbers: 1544/21

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED
• IPD Plan Description: Raw data may be made available through a controlled access procedures (privacy restrictions)

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No