NCT05506358

Evaluation of Low-cost Techniques for Detecting Sickle Cell Disease and β-thalassemia in Nepal and Canada

Completed NA Results posted Last updated 4 June 2024

What this trial tests

NA trial testing High performance liquid chromatography in Sickle Cell Disease in 145 participants. Completed in 30 March 2023.

Timeline

20 September 2022

Primary endpoint
30 March 2023

30 March 2023

Quick facts

Lead sponsor	University of British Columbia
Phase	NA
Status	Completed
Study type	INTERVENTIONAL
Allocation	na
Design	single group
Masking	none
Primary purpose	diagnostic
Enrollment	145
Start date	20 September 2022
Primary completion	30 March 2023
Estimated completion	30 March 2023
Sites	3 locations across Canada, Nepal

Drugs / interventions tested

• High performance liquid chromatography
• Automated sickling test
• HbS solubility test
• HemoTypeSC
• Sickle SCAN
• Gazelle Hb Variant Test

Conditions studied

• Sickle Cell Disease — all drugs for Sickle Cell Disease →
• Sickle Cell Trait — all drugs for Sickle Cell Trait →
• Beta-Thalassemia — all drugs for Beta-Thalassemia →
• Sickle Cell-Beta Thalassemia — all drugs for Sickle Cell-Beta Thalassemia →

Sponsor

University of British Columbia

Who can join

1 and older, any sex, with Sickle Cell Disease or Sickle Cell Trait. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Sensitivity, Specificity, Positive Predictive Value and Negative Predictive Value Primary · baseline

The following metrics will be determined for the low-cost tests to be evaluated as indicated below (where TP = true positive, TN = true negative, FP = false positive, FN = false negative): 1. Sensitivity = TP/(TP + FN) 2. Specificity = TN/(FP + TN) 3. Positive predictive value = TP/(TP + FP) 4. Negative predictive value = TN/(TN + FN) These metrics will be calculated for the low-cost technologies against the reference test, HPLC, for detecting the presence of sickle hemoglobin and β- thalassemia. The low-cost technologies include automated sickling test (standard sickling test enhanced using

Gazelle (sensitivity)

Group	Value	95% CI
HbSS	96.6
HbAS	100
HbS/β-thalassemia	0
HbA/β-thalassemia	91.3
HbAA	96.7

Gazelle (specificity)

Group	Value	95% CI
HbSS	89.9
HbAS	100
HbS/β-thalassemia	99.2
HbA/β-thalassemia	99.1
HbAA	98.1

Gazelle (PPV)

Group	Value	95% CI
HbSS	71.8
HbAS	100
HbS/β-thalassemia	0
HbA/β-thalassemia	95.5
HbAA	93.5

Gazelle (NPV)

Group	Value	95% CI
HbSS	99
HbAS	100
HbS/β-thalassemia	92
HbA/β-thalassemia	98.3
HbAA	99.1

HemoTypeSC (sensitivity)

Group	Value	95% CI
HbSS	100
HbAS	97.8
HbS/β-thalassemia	0
HbA/β-thalassemia	0
HbAA	100

HemoTypeSC (specificity)

Group	Value	95% CI
HbSS	89
HbAS	100
HbS/β-thalassemia	100
HbA/β-thalassemia	100
HbAA	78.7

HemoTypeSC (NPV)

Group	Value	95% CI
HbSS	100
HbAS	98.9
HbS/β-thalassemia	92
HbA/β-thalassemia	83.3
HbAA	100

Sickle SCAN (sensitivity)

Group	Value	95% CI
HbSS	100
HbAS	100
HbS/β-thalassemia	0
HbA/β-thalassemia	0
HbAA	100

Sponsor's own description

Sickle cell disease (SCD) is an inherited blood disorder associated with acute illness and organ damage. In high resource settings, early screening and treatment greatly improve quality of life. In low resource settings, however, mortality rate for children is high (50-90%). Low-cost and accurate screening techniques are critical to reducing the burden of the disease, especially in remote/rural settings. The most common and severe form of SCD is sickle cell anemia (SCA), caused by the inheritance of genes causing abnormal forms of hemoglobin (called sickle hemoglobin or hemoglobin S) from both parents. The asymptomatic or carrier form of the disease, known as sickle cell trait (SCT), is caused by the inheritance of only one variant gene from one of the parents. In areas such as Nepal, β-thalassemia (another inherited blood disorder) and SCD are both prevalent, and some combinations of these diseases lead to severe symptoms.

The purpose of this study is to determine the accuracy of low-cost point-of-care techniques for screening and detecting sickle cell disease, sickle cell trait, and β-thalassaemia, which will subsequently inform on feasible solutions for detecting the disease in rural, remote, or low-resource settings. One of the goals of the study is to evaluate the feasibility of techniques, such as the sickling test with low-cost microscopy and machine learning, HbS solubility test, commercial lateral-flow assays (HemoTypeSC and Sickle SCAN), and the Gazelle Hb variant test, to supplement or replace gold standard tests (HPLC or electrophoresis), which are expensive, require highly trained personnel, and are not easily accessible in remote/rural settings.

The investigators hypothesize that:

1. an automated sickling test (standard sickling test enhanced using low-cost microscopy and machine learning) has a higher overall accuracy than conventional screening techniques (solubility and sickling tests) to detect hemoglobin S in blood samples
2. the automated sickling test can additionally classify SCD, SCT and healthy individuals with a sensitivity greater than 90%, based on morphology changes of red blood cells, unlike conventional sickling or solubility tests that do not distinguish between SCD and SCT cases
3. Gazelle diagnostic device can detect β-thalassaemia and SCD/SCT with an overall accuracy greater than 90%, compared with HPLC as the reference test

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

1. Evaluation of low-cost techniques to detect sickle cell disease and β-thalassemia: an open-label, international, multicentre study.
   Shrestha P, Lohse H, Bhatla C, McCartney H, et al · · 2025 · cited 1× · PMID 40230447 · DOI 10.1016/j.lansea.2025.100571