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Evaluation of a Diagnostic to Identify Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency in Brazil

Primary Purpose

G6PD Deficiency

Status
Completed
Phase
Not Applicable
Locations
Brazil
Study Type
Interventional
Intervention
SD Biosensor STANDARD G6PD Test
Pointe Scientific Test Kit
HemoCue System
Complete blood count (CBC)
Sponsored by
PATH
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional other trial for G6PD Deficiency focused on measuring G6PD deficiency

Eligibility Criteria

2 Years - undefined (Child, Adult, Older Adult)All SexesAccepts Healthy Volunteers

  1. Participants with unknown G6PD status

    Inclusion criteria:

    • Febrile patients seeking care at the Manaus or Porto Velho clinics
    • 2 years age or older
    • Willing to provide informed consent

    Exclusion criteria

    • Younger than 2 years of age
    • Participants who received a blood transfusion in the last 3 months, self report
    • Unwilling to provide informed consent

  2. Participants with known G6PD status

    Inclusion criteria:

    • Included in previous G6PD surveys and provided consent to be contacted again
    • 2 years of age or older
    • Willing to provide informed consent or assent

    Exclusion criteria:

    • Younger than 2 years of age
    • Participants who received a blood transfusion in the last 3 months, self report
    • Unwilling to provide informed consent or assent or unavailable during study visit
  3. Health workers

Inclusion Criteria:

  • Provides malaria case management at study facility or study site
  • Considered an intended user of quantitative POC G6PD tests
  • Trained and proficient in the use of the POC G6PD test
  • Willing to provide informed consent

Exclusion Criteria:

  • Does not provide malaria case management at study facility or study site
  • Not considered an intended user of quantitative POC G6PD tests
  • Not trained or not proficient in the use of the POC G6PD test
  • Unwilling to provide informed consent

Sites / Locations

  • Tropical Medicine Foundation Doctor Heitor Vieira Dourado
  • Centro de Pesquisa em Medicina Tropical de Rondônia

Arms of the Study

Arm 1

Arm 2

Arm Type

Other

No Intervention

Arm Label

G6PD Diagnostic Testing

Health Workers

Arm Description

Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed the SD Biosensor STANDARD G6PD test and the POC HemoCue hemoglobin test on finger stick blood samples. At the reference laboratories, G6PD activity was measured from whole blood samples using the SD Biosensor STANDARD G6PD test and the Pointe Scientific G6PD reference assay and hemoglobin was measured using the HemoCue hemoglobin test and by a complete blood count (CBC) using an automated hematology analyzer (Manaus site only).

Participants were trained on use of the SD Biosensor STANDARD G6PD test by members of the study team with extensive experience with G6PD diagnostics and the STANDARD G6PD test. Health worker participants were surveyed to assess label and packing comprehension as well as results interpretation.

Outcomes

Primary Outcome Measures

Sensitivity of SD Biosensor STANDARD G6PD Test for Identifying G6PD Deficient Individuals
For the purposes of this study, an individual was considered G6PD deficient if they tested positive in the Pointe Scientific assay. A true positive was defined as a participant with ≤ 30% of normal G6PD activity in circulating venous blood determined by the Pointe Scientific test. Diagnostic sensitivity of the SD Biosensor STANDARD G6PD test is defined as the percentage of participants who tested positive for G6PD deficiency on the reference test who were identified by the test assay as positive, calculated as: Number of participants who were both test and true positive / (Number of participants who were test and true positive + Number of participants who were test negative but true positive [ie false negative]) * 100%. Sensitivity of the SD Biosensor STANDARD G6PD test was calculated from both venous and capillary blood samples.
Sensitivity of SD Biosensor STANDARD G6PD Test for Identifying Women With Intermediate G6PD Activity
To investigate the performance of the SD Biosensor STANDARD G6PD test to distinguish females with intermediate G6PD activity from females with normal activity, assay sensitivity was determined at a G6PD activity threshold of 70%. A true positive for intermediate G6PD activity in females was defined as G6PD activity between 30 and 70% of normal in circulating venous blood as determined by the Pointe Scientific test. Sensitivity of the SD Biosensor STANDARD G6PD test is the percentage of women who tested positive for intermediate G6PD activity on the reference test who were identified by the test assay as positive, calculated as: Number of women who were both test and true positive / (Number of women who were test and true positive + Number of women who were test negative but true positive [ie false negative]) * 100%. Sensitivity of the SD Biosensor STANDARD G6PD test for identifying females with intermediate G6PD activity was calculated from both venous and capillary blood samples.
Specificity of SD Biosensor STANDARD G6PD Test for Identifying G6PD Deficient Individuals
For the purposes of this study, an individual was considered G6PD deficient if they tested positive by the Pointe Scientific assay. A true negative was defined as > 30% of normal G6PD activity in circulating venous blood as determined by the Pointe Scientific test. Specificity is the percentage of participants who tested negative for G6PD deficiency on the reference test who were identified as negative using the test assay, calculated as: Number of participants who were both test and true negative / (Number of participants who were test and true negative + Number of participants who were test positive but true negative [ie false positive]) * 100%. Specificity of the SD Biosensor STANDARD G6PD test was calculated from both venous and capillary blood samples.
Specificity of SD Biosensor STANDARD G6PD Test for Identifying Women With Intermediate G6PD Activity
To investigate the performance of the SD Biosensor STANDARD G6PD test to distinguish females with intermediate G6PD activity from females with normal activity, the specificity was determined at a G6PD activity threshold of 70%. A true negative for intermediate G6PD activity in females was defined as G6PD activity > 70% of normal in circulating venous blood as determined by the Pointe Scientific test. Specificity is the percentage of participants who tested negative for G6PD deficiency on the reference test who were identified as negative using the test assay, calculated as: Number of participants who were both test and true negative / (Number of participants who were test and true negative + Number of participants who were test positive but true negative [ie false positive]) * 100%. Specificity of the SD Biosensor STANDARD G6PD test was calculated from both venous and capillary blood samples.

Secondary Outcome Measures

Accuracy Between the SD Biosensor STANDARD G6PD Test Assay and the Pointe Scientific Test Kit
Accuracy between the SD Biosensor STANDARD G6PD test assay and the Pointe Scientific G6PD reference assay was calculated as the percent agreement between both G6PD tests, ie, the percentage of participants with the same diagnosis according to both tests (either deficient, intermediate, or normal G6PD levels). Accuracy of the SD Biosensor STANDARD G6PD test was calculated from both venous and capillary blood samples.
Accuracy Between the SD Biosensor STANDARD G6PD Test Measure of Hemoglobin and the Reference HemoCue Hemoglobin Test
Accuracy between the SD Biosensor STANDARD G6PD test measure of hemoglobin and the HemoCue hemoglobin reference assay was calculated as the percentage agreement between both tests, ie, the percentage of participants with the same diagnosis according to both tests (either non/mild anemia, moderate anemia or severe anemia).
Accuracy Between the SD Biosensor STANDARD G6PD Test Measure of Hemoglobin and the Hemoglobin Measured in a Complete Blood Count
Accuracy between the SD Biosensor STANDARD G6PD test measure of hemoglobin and the hemoglobin result from the complete blood count (CBC) reference assay (using an automated hematology analyzer) was calculated as the percentage agreement between both tests, ie, the percentage of participants with the same diagnosis according to both tests (either non/mild anemia, moderate anemia or severe anemia). Complete blood counts were only conducted for participants enrolled at the site in Manaus.
Median G6PD Values Measured by the SD Biosensor STANDARD G6PD Test for Venous and Capillary Blood Samples
Number of Participants Who Met Acceptance Criteria for Label Comprehension
After completing training, health worker participants were asked to complete a questionnaire to assess their comprehension of the test label. The questionnaire consisted of 13 multiple-choice questions with mutually exclusive options and a single correct answer focused on aspects of the product label including key warnings, limitations, and restrictions as well as the proper test procedure. Acceptance (success) criterion for label comprehension was defined as at least 85% correct responses (11 out of 13 possible points).
Number of Participants Who Met Acceptance Criteria for Accurate Results Interpretation
After completing training, health worker participants were asked to complete a questionnaire to assess their ability to interpret the test result outputs. The questionnaire consisted of seven short-answer questions (5 valid results, 2 invalid results) focused on the participant's ability to read the results screen, record the simulated G6PD and hemoglobin quantitative results, and classify the results as normal, intermediate, deficient, or invalid. For each valid result, three points were possible: (one for G6PD result transcription, one for hemoglobin result transcription, and one for result interpretation) and for each invalid result, one point was possible, resulting in a total of 17 possible points. Acceptance (success) criterion for results interpretation was defined as at least 85% correct responses (15 out of 17 possible points).

Full Information

First Posted
July 17, 2019
Last Updated
October 13, 2021
Sponsor
PATH
Collaborators
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado
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1. Study Identification

Unique Protocol Identification Number
NCT04033640
Brief Title
Evaluation of a Diagnostic to Identify Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency in Brazil
Official Title
Evaluation of a Diagnostic to Identify G6PD Deficiency in Brazil
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
June 27, 2019 (Actual)
Primary Completion Date
December 31, 2019 (Actual)
Study Completion Date
December 31, 2019 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
PATH
Collaborators
Fundação de Medicina Tropical Dr. Heitor Vieira Dourado

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
No

5. Study Description

Brief Summary
Th objectives of this study are: To determine the performance of G6PD tests in detecting G6PD activity and hemoglobin (Hb) compared to a reference assay To assess the comprehension of the G6PD test packaging and labelling among intended users To assess the usability of G6PD test result outputs among intended users
Detailed Description
This is a cross-sectional diagnostic accuracy study that includes both participants and health worker participants. The participant population will be recruited at clinics and through a household survey using an enriched sample of a population with known G6PD status, established through previous epidemiological studies. Clinic staff will take capillary blood samples and conduct two point of care (POC) tests: 1) HemoCue® hemoglobin test, and 2) the investigational Standard Diagnostics (SD) Biosensor STANDARD POC test for glucose-6-phosphate dehydrogenase (G6PD) deficiency. Venous blood will be collected and transferred to a laboratory where reference assays will be performed on venous samples using the Pointe Scientific G6PD Analyzer and hemoglobin tests. The health worker participants will include trained intended users of the G6PD tests. Trained health workers will be surveyed to assess product usability through a questionnaire to assess label and packing comprehension as well as results interpretation.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
G6PD Deficiency
Keywords
G6PD deficiency

7. Study Design

Primary Purpose
Other
Study Phase
Not Applicable
Interventional Study Model
Parallel Assignment
Masking
None (Open Label)
Allocation
Non-Randomized
Enrollment
1754 (Actual)

8. Arms, Groups, and Interventions

Arm Title
G6PD Diagnostic Testing
Arm Type
Other
Arm Description
Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed the SD Biosensor STANDARD G6PD test and the POC HemoCue hemoglobin test on finger stick blood samples. At the reference laboratories, G6PD activity was measured from whole blood samples using the SD Biosensor STANDARD G6PD test and the Pointe Scientific G6PD reference assay and hemoglobin was measured using the HemoCue hemoglobin test and by a complete blood count (CBC) using an automated hematology analyzer (Manaus site only).
Arm Title
Health Workers
Arm Type
No Intervention
Arm Description
Participants were trained on use of the SD Biosensor STANDARD G6PD test by members of the study team with extensive experience with G6PD diagnostics and the STANDARD G6PD test. Health worker participants were surveyed to assess label and packing comprehension as well as results interpretation.
Intervention Type
Diagnostic Test
Intervention Name(s)
SD Biosensor STANDARD G6PD Test
Intervention Description
The SD Biosensor G6PD Analyzer is designed to measure the quantitative determination of total hemoglobin concentration and G6PD enzymatic activity in fresh human whole blood specimens based on reflectometry assays in a point-of-care (POC) setting. The test is intended to aid in the identification of people with G6PD deficiency. The test is currently not licensed for use in Brazil and is considered an investigational product.
Intervention Type
Diagnostic Test
Intervention Name(s)
Pointe Scientific Test Kit
Intervention Description
The Pointe Scientific test kit will serve as the reference assay to assess G6PD activity. Its intended use is for the quantitative, kinetic determination of G6PD in blood at 340 nm.
Intervention Type
Diagnostic Test
Intervention Name(s)
HemoCue System
Intervention Description
The HemoCue hemoglobin (Hb) 201+ system is designed for quantitative point-of-care whole blood hemoglobin determination in primary care using a specially designed analyzer, the HemoCue Hb 201+ Analyzer, and specially designed microcuvettes, the HemoCue Hb 201+Microcuvettes.
Intervention Type
Diagnostic Test
Intervention Name(s)
Complete blood count (CBC)
Intervention Description
In Manaus, hemoglobin concentration was determined by CBC using an automated hematology analyzer (Sysmex KX-21N).
Primary Outcome Measure Information:
Title
Sensitivity of SD Biosensor STANDARD G6PD Test for Identifying G6PD Deficient Individuals
Description
For the purposes of this study, an individual was considered G6PD deficient if they tested positive in the Pointe Scientific assay. A true positive was defined as a participant with ≤ 30% of normal G6PD activity in circulating venous blood determined by the Pointe Scientific test. Diagnostic sensitivity of the SD Biosensor STANDARD G6PD test is defined as the percentage of participants who tested positive for G6PD deficiency on the reference test who were identified by the test assay as positive, calculated as: Number of participants who were both test and true positive / (Number of participants who were test and true positive + Number of participants who were test negative but true positive [ie false negative]) * 100%. Sensitivity of the SD Biosensor STANDARD G6PD test was calculated from both venous and capillary blood samples.
Time Frame
All samples were collected on study day 1
Title
Sensitivity of SD Biosensor STANDARD G6PD Test for Identifying Women With Intermediate G6PD Activity
Description
To investigate the performance of the SD Biosensor STANDARD G6PD test to distinguish females with intermediate G6PD activity from females with normal activity, assay sensitivity was determined at a G6PD activity threshold of 70%. A true positive for intermediate G6PD activity in females was defined as G6PD activity between 30 and 70% of normal in circulating venous blood as determined by the Pointe Scientific test. Sensitivity of the SD Biosensor STANDARD G6PD test is the percentage of women who tested positive for intermediate G6PD activity on the reference test who were identified by the test assay as positive, calculated as: Number of women who were both test and true positive / (Number of women who were test and true positive + Number of women who were test negative but true positive [ie false negative]) * 100%. Sensitivity of the SD Biosensor STANDARD G6PD test for identifying females with intermediate G6PD activity was calculated from both venous and capillary blood samples.
Time Frame
All samples were collected on study day 1
Title
Specificity of SD Biosensor STANDARD G6PD Test for Identifying G6PD Deficient Individuals
Description
For the purposes of this study, an individual was considered G6PD deficient if they tested positive by the Pointe Scientific assay. A true negative was defined as > 30% of normal G6PD activity in circulating venous blood as determined by the Pointe Scientific test. Specificity is the percentage of participants who tested negative for G6PD deficiency on the reference test who were identified as negative using the test assay, calculated as: Number of participants who were both test and true negative / (Number of participants who were test and true negative + Number of participants who were test positive but true negative [ie false positive]) * 100%. Specificity of the SD Biosensor STANDARD G6PD test was calculated from both venous and capillary blood samples.
Time Frame
All samples were collected on study day 1
Title
Specificity of SD Biosensor STANDARD G6PD Test for Identifying Women With Intermediate G6PD Activity
Description
To investigate the performance of the SD Biosensor STANDARD G6PD test to distinguish females with intermediate G6PD activity from females with normal activity, the specificity was determined at a G6PD activity threshold of 70%. A true negative for intermediate G6PD activity in females was defined as G6PD activity > 70% of normal in circulating venous blood as determined by the Pointe Scientific test. Specificity is the percentage of participants who tested negative for G6PD deficiency on the reference test who were identified as negative using the test assay, calculated as: Number of participants who were both test and true negative / (Number of participants who were test and true negative + Number of participants who were test positive but true negative [ie false positive]) * 100%. Specificity of the SD Biosensor STANDARD G6PD test was calculated from both venous and capillary blood samples.
Time Frame
All samples were collected on study day 1
Secondary Outcome Measure Information:
Title
Accuracy Between the SD Biosensor STANDARD G6PD Test Assay and the Pointe Scientific Test Kit
Description
Accuracy between the SD Biosensor STANDARD G6PD test assay and the Pointe Scientific G6PD reference assay was calculated as the percent agreement between both G6PD tests, ie, the percentage of participants with the same diagnosis according to both tests (either deficient, intermediate, or normal G6PD levels). Accuracy of the SD Biosensor STANDARD G6PD test was calculated from both venous and capillary blood samples.
Time Frame
All samples were collected on study day 1
Title
Accuracy Between the SD Biosensor STANDARD G6PD Test Measure of Hemoglobin and the Reference HemoCue Hemoglobin Test
Description
Accuracy between the SD Biosensor STANDARD G6PD test measure of hemoglobin and the HemoCue hemoglobin reference assay was calculated as the percentage agreement between both tests, ie, the percentage of participants with the same diagnosis according to both tests (either non/mild anemia, moderate anemia or severe anemia).
Time Frame
All samples were collected on study day 1
Title
Accuracy Between the SD Biosensor STANDARD G6PD Test Measure of Hemoglobin and the Hemoglobin Measured in a Complete Blood Count
Description
Accuracy between the SD Biosensor STANDARD G6PD test measure of hemoglobin and the hemoglobin result from the complete blood count (CBC) reference assay (using an automated hematology analyzer) was calculated as the percentage agreement between both tests, ie, the percentage of participants with the same diagnosis according to both tests (either non/mild anemia, moderate anemia or severe anemia). Complete blood counts were only conducted for participants enrolled at the site in Manaus.
Time Frame
All samples were collected on study day 1
Title
Median G6PD Values Measured by the SD Biosensor STANDARD G6PD Test for Venous and Capillary Blood Samples
Time Frame
All samples were collected on study day 1
Title
Number of Participants Who Met Acceptance Criteria for Label Comprehension
Description
After completing training, health worker participants were asked to complete a questionnaire to assess their comprehension of the test label. The questionnaire consisted of 13 multiple-choice questions with mutually exclusive options and a single correct answer focused on aspects of the product label including key warnings, limitations, and restrictions as well as the proper test procedure. Acceptance (success) criterion for label comprehension was defined as at least 85% correct responses (11 out of 13 possible points).
Time Frame
Day 1
Title
Number of Participants Who Met Acceptance Criteria for Accurate Results Interpretation
Description
After completing training, health worker participants were asked to complete a questionnaire to assess their ability to interpret the test result outputs. The questionnaire consisted of seven short-answer questions (5 valid results, 2 invalid results) focused on the participant's ability to read the results screen, record the simulated G6PD and hemoglobin quantitative results, and classify the results as normal, intermediate, deficient, or invalid. For each valid result, three points were possible: (one for G6PD result transcription, one for hemoglobin result transcription, and one for result interpretation) and for each invalid result, one point was possible, resulting in a total of 17 possible points. Acceptance (success) criterion for results interpretation was defined as at least 85% correct responses (15 out of 17 possible points).
Time Frame
Day 1

10. Eligibility

Sex
All
Minimum Age & Unit of Time
2 Years
Accepts Healthy Volunteers
Accepts Healthy Volunteers
Eligibility Criteria
Participants with unknown G6PD status Inclusion criteria: Febrile patients seeking care at the Manaus or Porto Velho clinics 2 years age or older Willing to provide informed consent Exclusion criteria Younger than 2 years of age Participants who received a blood transfusion in the last 3 months, self report Unwilling to provide informed consent Participants with known G6PD status Inclusion criteria: Included in previous G6PD surveys and provided consent to be contacted again 2 years of age or older Willing to provide informed consent or assent Exclusion criteria: Younger than 2 years of age Participants who received a blood transfusion in the last 3 months, self report Unwilling to provide informed consent or assent or unavailable during study visit Health workers Inclusion Criteria: Provides malaria case management at study facility or study site Considered an intended user of quantitative POC G6PD tests Trained and proficient in the use of the POC G6PD test Willing to provide informed consent Exclusion Criteria: Does not provide malaria case management at study facility or study site Not considered an intended user of quantitative POC G6PD tests Not trained or not proficient in the use of the POC G6PD test Unwilling to provide informed consent
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Marcus Lacerda, MD, PhD
Organizational Affiliation
FMT/HVD
Official's Role
Principal Investigator
Facility Information:
Facility Name
Tropical Medicine Foundation Doctor Heitor Vieira Dourado
City
Manaus
State/Province
Amazonas
Country
Brazil
Facility Name
Centro de Pesquisa em Medicina Tropical de Rondônia
City
Porto Velho
State/Province
Rondônia
Country
Brazil

12. IPD Sharing Statement

Plan to Share IPD
No
IPD Sharing Plan Description
There is no plan to share any IPD with other researchers.
Citations:
PubMed Identifier
34383774
Citation
Zobrist S, Brito M, Garbin E, Monteiro WM, Clementino Freitas S, Macedo M, Soares Moura A, Advani N, Kahn M, Pal S, Gerth-Guyette E, Bansil P, Domingo GJ, Pereira D, Lacerda MV. Evaluation of a point-of-care diagnostic to identify glucose-6-phosphate dehydrogenase deficiency in Brazil. PLoS Negl Trop Dis. 2021 Aug 12;15(8):e0009649. doi: 10.1371/journal.pntd.0009649. eCollection 2021 Aug.
Results Reference
derived
PubMed Identifier
34238299
Citation
Gerth-Guyette E, Adissu W, Brito M, Garbin E, Macedo M, Sharma A, Das S, Lacerda MVG, Pereira D, Talukdar A, Yilma D, Pal S, Zobrist S, Domingo GJ. Usability of a point-of-care diagnostic to identify glucose-6-phosphate dehydrogenase deficiency: a multi-country assessment of test label comprehension and results interpretation. Malar J. 2021 Jul 8;20(1):307. doi: 10.1186/s12936-021-03803-1.
Results Reference
derived

Learn more about this trial

Evaluation of a Diagnostic to Identify Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency in Brazil

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