Sysmex-XN 20 Analyser to Assess Lymphocyte Subsets and Other Haematological Parameters in Chronic/Acute Viral Infections (SASA)

An Observational Study Exploring the Utility of the Sysmex-XN 20 Analyser to Assess Lymphocyte Subsets and Other Haematological Parameters in Chronic or Acute Viral Infections,

The XN-20, is a full blood count (FBC) analyser with an extended differential counting and flagging System. The XN-Series' individual channels allow real-time reflex analysis, and uses a two stage process to classify the white blood count (WBC) sub-populations and detect the presence of abnormal reactive and malignant cells. In regards to lymphocytes in the peripheral blood, the machine has the capacity to distinguish activated from non-activated T-cell subsets using a very small volume of EDTA sample (88uL) (including remnant sample from a standard full blood count) with results available in 1.5 minutes. It is a fully automated process and can be considered as an alternative rapid flow cytometry method.

Objective of the SASA study: to investigate the signal pattern of white blood cells assessed using the XN-20 full blood count platform in patients with untreated viral infections i.e. HIV, HCV and HBV. The data from the analysis will be reviewed in conjunction with patient's demographic and clinical disease characteristics with the aim of detecting characteristic cell populations that can be used in the development of system flags for future studies.

Study Overview

• Status: Unknown
• Conditions: Chronic Hepatitis C; Diagnostic; Chronic HIV Infection; Chronic Viral Hepatitis B
• Intervention / Treatment: Diagnostic test: blood draw

Detailed Description

Study design: observational pilot study. Approximately one hundred, participants (25 in each of group, A to D), will be enrolled at a single clinical site.

Study question: Do participants who have chronic or acute viral infections i.e. untreated HIV, HIV-HCV with treated HIV and untreated HCV, untreated HCV monoinfection or untreated HBV monoinfection, have a significant excess of activated lymphocytes as measured by D1+D2 on the XN WDF channel using the XN-20 analyser?

Objectives:

Primary: To assess whether participants who have chronic or acute viral infections have a significant excess of activated lymphocytes measured by the Sysmex-XN 20 analyser.

Secondary: To compare, the absolute numbers and percentages of lymphocytes subsets as measured in the Sysmex-XN 20 analyser to the percentages of these cells when measured using standard laboratory methods i.e. flow cytometry.

Primary Outcome Measure(s): Percentage of lymphocytes measured in area D1+D2 of the XN WDF and W1/W2 ratio from the WPC channel.

Secondary Outcome Measure(s ):

1. % lymphocytes in the D1 area of the XN WDF channel;
2. % lymphocytes in the D2 area of the XN WDF channel;
3. % lymphocytes in the D0 area of the XN WDF channel;
4. correlation between CD4+ T-cells (as measured by standard flow cytometry) and the D1+D2 area on the XN WDF channel;
5. correlation between CD8+ T-cells (as measured by standard flow cytometry) and the D1+D2 area on the XN WDF channel;
6. correlation between CD4+ T-cells (as measured by standard flow cytometry) and the W1/W2 area on the XN WPC channel;
7. correlation between CD8+ T-cells (as measured by standard flow cytometry) and the W1/W2 area on the XN WPC channel;

Exploratory:

Association of uncontrolled viral infection and the following as measured on the XN-20 platform

• % of lymphocytes mainly synthesizing antibodies with high fluorescence intensity (AS-Lymph);
• absolute and % lymphocytes reacting to infection with high fluorescence intensity (RE-Lymph);
• % reactive monocytes
• Neutrophil reactivity intensity;
• Neutrophil granularity intensity;
• Immature platelet fraction;
• Comparison of the blood film (DI-60 Review) and selected WBC subset read outs from the XN-20.
• Review of WDF lymphocyte cloud positional information using - HFLC/LY-X/LY-Y/LY-Z/LY-WX/LY-WY/LY-WZ.

• Study Type: Observational
• Enrollment (Anticipated): 100

Contacts and Locations

• Study Contact: Name: Sarah L Pett, MD/PhD; Phone Number: +44 (0)798 380 6215; Email: s.pett@ucl.ac.uk
• Study Contact Backup: Name: Andrea Cartier, BA; Phone Number: +44 (0)203 108 2081; Email: a.cartier@ucl.ac.uk

Study Locations

• United Kingdom
  • London, United Kingdom, WC1E 6JB
    • Mortimer Market Centre
    • Contact: Sarah L Pett, MD/PhD; Phone Number: 0203 108 2081; Email: s.pett@ucl.ac.uk
    • Contact: Andrea Cartier, BA; Phone Number: 0203 108 2081; Email: a.cartier@ucl.ac.uk
    • Principal Investigator: Sarah L Pett, MD/PhD
    • Sub-Investigator: Lewis Haddow, MD/PhD
    • Sub-Investigator: Erica Pool, MD
    • Sub-Investigator: Diarmuid Nugent, MD
    • Sub-Investigator: Binta Sultan, MD

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

• Sampling Method: Non-Probability Sample

Study Population

Four groups of participants with chronic or acute viral infections :1) Group A: untreated Human Immunodeficiency Virus (HIV)-infected; 2) Group B: HIV-hepatitis C (HIV/HCV) coinfected, with treated HIV but untreated HCV; 3) Group C: untreated HCV monoinfection; 4) Group D: untreated Hepatitis B (HBV) monoinfection.

Description

Inclusion Criteria:

• Adults aged ≥18 years;
• Registered patient at Mortimer Market Centre;
• Willing to have a blood draw for the purpose of the study or, if the participant is having a blood draw for routine care, willing to have an additional EDTA sample taken at the time of that routine blood draw and willing that the results of the sample being drawn for standard care (FBC and T-cell subsets) can be used for this study;

In one of the four mutually exclusive groups:

i) Group A: HIV-infected (chronic or acute infection) with a HIV viral load of >1000 copies/mL in the 6 months prior to study entry and not (yet) in receipt of combination antiretroviral therapy (cART) at study entry; ii) Group B: HIV-infected on cART with HIV viral load <50 copies/mL within the 6 months prior to study entry, at least one measure of HCV (chronic or acute infection) showing a detectable HCV viral load and not in receipt of HCV treatment at study entry; iii) Group C: HCV mono-infected (chronic or acute infection) with detectable HCV viral load (>lower limit of quantification) in the prior 6 months and not in receipt of HCV treatment at study entry; iv) Group D: HBV mono-infected (chronic or acute infection) patients with detectable HBV viral load in the prior 6 months and not in receipt of HBV treatment at study entry.

- written informed consent.

Exclusion Criteria:

• On immunosuppressants and/or receiving chemotherapy or radiotherapy for a malignancy;
• Intercurrent infection within the prior 30 days (e.g. influenza like illness).

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

4

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
A; HIV-infected (chronic or acute infection) with a HIV viral load of >1000 copies/mL in the 6 months prior to study entry and not (yet) in receipt of combination antiretroviral therapy (cART) at study entry.	Diagnostic test: blood draw; single one time blood draw to measure lymphocyte panels included activated lymphocytes using remnant sample from a full blood count; Other Names: lymphocytes panels as measured by Sysmex XN-20 analyser
B; HIV-infected on cART with HIV viral load <50 copies/mL within the 6 months prior to study entry, at least one measure of HCV (chronic or acute infection) showing a detectable HCV viral load and not in receipt of HCV treatment at study entry.	Diagnostic test: blood draw; single one time blood draw to measure lymphocyte panels included activated lymphocytes using remnant sample from a full blood count; Other Names: lymphocytes panels as measured by Sysmex XN-20 analyser
C; HCV mono-infected (chronic or acute infection) with detectable HCV viral load (>lower limit of quantification) in the prior 6 months and not in receipt of HCV treatment at study entry.	Diagnostic test: blood draw; single one time blood draw to measure lymphocyte panels included activated lymphocytes using remnant sample from a full blood count; Other Names: lymphocytes panels as measured by Sysmex XN-20 analyser
D; HBV mono-infected (chronic or acute infection) patients with detectable HBV viral load in the prior 6 months and not in receipt of HBV treatment at study entry.	Diagnostic test: blood draw; single one time blood draw to measure lymphocyte panels included activated lymphocytes using remnant sample from a full blood count; Other Names: lymphocytes panels as measured by Sysmex XN-20 analyser

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Time Frame
Percentage of lymphocytes measured in area D1+D2 of the XN WDF and W1/W2 ratio from the WPC channel.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
% lymphocytes in the D1 and D2 area of the XN WDF channel	as above	Day 1
% lymphocytes in the D0 area of the XN WDF channel;	as above	Day 1
correlation between CD4+ T-cells (as measured by standard flow cytometry) and the D1+D2 area on the XN WDF channel;	as above	Day 1
correlation between CD8+ T-cells (as measured by standard flow cytometry) and the D1+D2 area on the XN WDF channel;	as above	Day 1
correlation between CD4+ T-cells (as measured by standard flow cytometry) and the W1/W2 area on the XN WPC channel;	as above	Day 1
correlation between CD8+ T-cells (as measured by standard flow cytometry) and the W1/W2 area on the XN WPC channel;	as above	Day 1

Collaborators and Investigators

• Sponsor: University College, London
• Collaborators: Central and North West London NHS Foundation Trust
• Investigators: Study Chair: Sarah L Pett, MD/PhD, University College, London

Study record dates

Study Major Dates

• Study Start (Anticipated): April 15, 2018
• Primary Completion (Anticipated): August 15, 2018
• Study Completion (Anticipated): October 15, 2018

Study Registration Dates

• First Submitted: March 21, 2018
• First Submitted That Met QC Criteria: April 4, 2018
• First Posted (Actual): April 12, 2018

Study Record Updates

• Last Update Posted (Actual): April 12, 2018
• Last Update Submitted That Met QC Criteria: April 4, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: immunological
• Additional Relevant MeSH Terms: Digestive System Diseases; Pathologic Processes; RNA Virus Infections; Blood-Borne Infections; Disease Attributes; Liver Diseases; Flaviviridae Infections; Hepatitis, Viral, Human; Hepadnaviridae Infections; DNA Virus Infections; Enterovirus Infections; Picornaviridae Infections; Hepatitis, Chronic; Infections; Communicable Diseases; Hepatitis B; Hepatitis; Hepatitis A; Hepatitis C; Virus Diseases; Hepatitis B, Chronic; Hepatitis C, Chronic
• Other Study ID Numbers: UCL 17/0634

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No
• IPD Plan Description: We aim to recruit 100 participants in total, which will give us twenty-five participants per group. This is a convenience sample size that considered reasonable for this pilot, and can be recruited in the time frame allowed for this study, approximately 6 months. A simple descriptive analysis of data collected from the convenience sample will be presented. It is planned that results of this study will be published following its completion. There is no plan to inform participants of their individual data. The rationale for this is that this is an experimental testing platform, and it is unknown what the findings mean in the context of an individual participants' medical care. However, a letter summarising the group data will be developed and following approval by the IRB, given to all participants.

Drug and device information, study documents

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