Trial Outcomes & Findings for Evaluation of a Diagnostic to Identify Glucose-6-phosphate Dehydrogenase (G6PD) Deficiency in Brazil (NCT NCT04033640)

NCT ID: NCT04033640

Last Updated: 2021-11-11

Results Overview

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.

Recruitment status

COMPLETED

Study phase

NA

Target enrollment

1754 participants

Primary outcome timeframe

All samples were collected on study day 1

Results posted on

2021-11-11

Participant Flow

This diagnostic accuracy study was conducted at 2 centers situated in the Brazilian Amazon and included both participants and health workers. Participants were recruited at clinics and through an enriched sample in Manaus and Porto Velho, Brazil. Health worker participants included both health care providers, such as community health workers/field agents, and laboratory technicians who perform malaria rapid diagnostic tests and other malaria testing near the point of care (POC).

Participant milestones

Participant milestones
Measure
G6PD Diagnostic Testing
Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed the Standard Diagnostics (SD) Biosensor STANDARD glucose-6-phosphate dehydrogenase (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).
Health Workers
Participants were trained on use of the 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.
Overall Study
STARTED
1736
18
Overall Study
COMPLETED
1736
18
Overall Study
NOT COMPLETED
0
0

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

Demographic information were not collected for the health worker participants in this study.

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure
G6PD Diagnostic Testing
n=1736 Participants
Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed 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 CBC.
Health Workers
n=18 Participants
Participants were trained on use of the 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.
Total
n=1754 Participants
Total of all reporting groups
Age, Continuous
37.7 years
STANDARD_DEVIATION 13.9 • n=1736 Participants • Demographic information were not collected for the health worker participants in this study.
37.7 years
STANDARD_DEVIATION 13.9 • n=1736 Participants • Demographic information were not collected for the health worker participants in this study.
Age, Customized
2-11 years
24 Participants
n=1736 Participants • Demographic information were not collected for the health worker participants in this study.
24 Participants
n=1736 Participants • Demographic information were not collected for the health worker participants in this study.
Age, Customized
12-15 years
22 Participants
n=1736 Participants • Demographic information were not collected for the health worker participants in this study.
22 Participants
n=1736 Participants • Demographic information were not collected for the health worker participants in this study.
Age, Customized
16-64 years
1632 Participants
n=1736 Participants • Demographic information were not collected for the health worker participants in this study.
1632 Participants
n=1736 Participants • Demographic information were not collected for the health worker participants in this study.
Age, Customized
65+ years
58 Participants
n=1736 Participants • Demographic information were not collected for the health worker participants in this study.
58 Participants
n=1736 Participants • Demographic information were not collected for the health worker participants in this study.
Sex: Female, Male
Female
948 Participants
n=1736 Participants • Demographic information were not collected for the health worker participants in this study.
948 Participants
n=1736 Participants • Demographic information were not collected for the health worker participants in this study.
Sex: Female, Male
Male
788 Participants
n=1736 Participants • Demographic information were not collected for the health worker participants in this study.
788 Participants
n=1736 Participants • Demographic information were not collected for the health worker participants in this study.
Race and Ethnicity Not Collected
0 Participants
Race and Ethnicity were not collected from any participant.
Region of Enrollment
Brazil
1736 participants
n=1736 Participants
18 participants
n=18 Participants
1754 participants
n=1754 Participants

PRIMARY outcome

Timeframe: All samples were collected on study day 1

Population: Participants with available data

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.

Outcome measures

Outcome measures
Measure
G6PD Diagnostic Testing
n=1693 Participants
Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed 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 CBC.
Sensitivity of SD Biosensor STANDARD G6PD Test for Identifying G6PD Deficient Individuals
Venous blood
100.0 percentage of participants
Interval 93.6 to 100.0
Sensitivity of SD Biosensor STANDARD G6PD Test for Identifying G6PD Deficient Individuals
Capillary blood
100.0 percentage of participants
Interval 93.8 to 100.0

PRIMARY outcome

Timeframe: All samples were collected on study day 1

Population: Female participants with available data

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.

Outcome measures

Outcome measures
Measure
G6PD Diagnostic Testing
n=918 Participants
Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed 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 CBC.
Sensitivity of SD Biosensor STANDARD G6PD Test for Identifying Women With Intermediate G6PD Activity
Venous blood
96.9 percentage of participants
Interval 83.8 to 99.9
Sensitivity of SD Biosensor STANDARD G6PD Test for Identifying Women With Intermediate G6PD Activity
Capillary blood
94.3 percentage of participants
Interval 80.8 to 99.3

PRIMARY outcome

Timeframe: All samples were collected on study day 1

Population: Participants with available data

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.

Outcome measures

Outcome measures
Measure
G6PD Diagnostic Testing
n=1693 Participants
Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed 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 CBC.
Specificity of SD Biosensor STANDARD G6PD Test for Identifying G6PD Deficient Individuals
Venous blood
98.6 percentage of participants
Interval 97.9 to 99.1
Specificity of SD Biosensor STANDARD G6PD Test for Identifying G6PD Deficient Individuals
Capillary blood
97.8 percentage of participants
Interval 97.0 to 98.5

PRIMARY outcome

Timeframe: All samples were collected on study day 1

Population: Female participants with available data

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.

Outcome measures

Outcome measures
Measure
G6PD Diagnostic Testing
n=918 Participants
Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed 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 CBC.
Specificity of SD Biosensor STANDARD G6PD Test for Identifying Women With Intermediate G6PD Activity
Venous blood
96.5 percentage of participants
Interval 95.0 to 97.6
Specificity of SD Biosensor STANDARD G6PD Test for Identifying Women With Intermediate G6PD Activity
Capillary blood
92.3 percentage of participants
Interval 90.3 to 94.0

SECONDARY outcome

Timeframe: All samples were collected on study day 1

Population: Participants with available data

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.

Outcome measures

Outcome measures
Measure
G6PD Diagnostic Testing
n=1693 Participants
Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed 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 CBC.
Accuracy Between the SD Biosensor STANDARD G6PD Test Assay and the Pointe Scientific Test Kit
Venous blood
96.7 percentage of participants
Interval 95.7 to 97.5
Accuracy Between the SD Biosensor STANDARD G6PD Test Assay and the Pointe Scientific Test Kit
Capillary blood
94.1 percentage of participants
Interval 92.9 to 95.2

SECONDARY outcome

Timeframe: All samples were collected on study day 1

Population: Participants with available data

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).

Outcome measures

Outcome measures
Measure
G6PD Diagnostic Testing
n=1693 Participants
Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed 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 CBC.
Accuracy Between the SD Biosensor STANDARD G6PD Test Measure of Hemoglobin and the Reference HemoCue Hemoglobin Test
Venous blood
93.3 percentage of participants
Interval 92.0 to 94.5
Accuracy Between the SD Biosensor STANDARD G6PD Test Measure of Hemoglobin and the Reference HemoCue Hemoglobin Test
Capillary blood
91.8 percentage of participants
Interval 90.4 to 93.1

SECONDARY outcome

Timeframe: All samples were collected on study day 1

Population: Participants enrolled at the site in Manaus with available data

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.

Outcome measures

Outcome measures
Measure
G6PD Diagnostic Testing
n=900 Participants
Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed 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 CBC.
Accuracy Between the SD Biosensor STANDARD G6PD Test Measure of Hemoglobin and the Hemoglobin Measured in a Complete Blood Count
Venous blood
93.1 percentage of participants
Interval 91.1 to 94.7
Accuracy Between the SD Biosensor STANDARD G6PD Test Measure of Hemoglobin and the Hemoglobin Measured in a Complete Blood Count
Capillary blood
93.2 percentage of participants
Interval 91.4 to 94.8

SECONDARY outcome

Timeframe: All samples were collected on study day 1

Population: Participants with available data

Outcome measures

Outcome measures
Measure
G6PD Diagnostic Testing
n=1735 Participants
Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed 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 CBC.
Median G6PD Values Measured by the SD Biosensor STANDARD G6PD Test for Venous and Capillary Blood Samples
Venous blood
8.0 units / gram of hemoglobin
Interval 7.1 to 9.1
Median G6PD Values Measured by the SD Biosensor STANDARD G6PD Test for Venous and Capillary Blood Samples
Capillary blood
7.6 units / gram of hemoglobin
Interval 6.6 to 8.8

SECONDARY outcome

Timeframe: Day 1

Population: Health worker participants

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).

Outcome measures

Outcome measures
Measure
G6PD Diagnostic Testing
n=18 Participants
Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed 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 CBC.
Number of Participants Who Met Acceptance Criteria for Label Comprehension
10 Participants

SECONDARY outcome

Timeframe: Day 1

Population: Health worker participants

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).

Outcome measures

Outcome measures
Measure
G6PD Diagnostic Testing
n=18 Participants
Participants provided whole blood samples as well as finger-stick capillary blood samples. At the clinic site, study staff performed 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 CBC.
Number of Participants Who Met Acceptance Criteria for Accurate Results Interpretation
16 Participants

Adverse Events

G6PD Diagnostic Testing

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Health Workers

Serious events: 0 serious events
Other events: 0 other events
Deaths: 0 deaths

Serious adverse events

Adverse event data not reported

Other adverse events

Adverse event data not reported

Additional Information

Pooja Bansil

PATH

Phone: 206 302 4920

Results disclosure agreements

  • Principal investigator is a sponsor employee
  • Publication restrictions are in place