Validation of a Jaundice Diagnostic and Monitoring Device for Low-Resource Settings

Validation of a Low-Cost, Point-of-Care Bilirubin Measurement to Diagnose Neonatal Jaundice and Monitor Phototherapy in Hospitals in Sub-Saharan Africa

A team of researchers at Rice University in partnership with clinicians at Queen Elizabeth Central Hospital created BiliSpec, a low-cost battery-powered reader designed to immediately quantify serum bilirubin levels from a small drop of whole blood applied to a lateral flow strip. The simple and affordable BiliSpec system offers a faster and more cost-effective means to detect neonatal jaundice in under-resourced clinics and determine when phototherapy is needed. The goal of this study is to validate the accuracy of the BiliSpec device in measuring bilirubin levels in neonates relative to the laboratory spectrophotometric bilirubinometer and transcutaneous bilirubinometer measurements.

Study Overview

• Status: Recruiting
• Conditions: Hyperbilirubinemia, Neonatal; Jaundice, Neonatal
• Intervention / Treatment: Diagnostic test: BiliSpec

Detailed Description

This study will validate the accuracy of the BiliSpec device in measuring bilirubin levels in neonates relative to a laboratory spectrophotometric bilirubinometer (Reichert UNISTAT® Bilirubinometer) and transcutaneous bilirubinometer measurements.

This study will enroll up to 500 neonates at Queen Elizabeth Central Hospital and Kamuzu Central Hospital each, for a total of up to 1000 neonates, at risk for jaundice based on clinical signs and symptoms or undergoing phototherapy for treatment of jaundice. During the pilot study, 100 participants were evaluated and 147 samples total were collected. However only 7 samples collected were over 20 mg/dL. In addition to confirming the accuracy of BiliSpec in this validation study, enough samples of clinically high bilirubin concentrations (>20mg/dL) will need to be collected to ensure the device functions properly over the intended dynamic range (0-35 mg/dL). To accomplish this, data from up to 500 participants at each location will be collected.

Informed consent will be requested from the parents of all eligible babies on the ward for this study. If the guardian does not consent, the patient's bilirubin levels will be assessed using the standard of care on the ward.

During the study, the following steps will be taken:

The trained study nurse will assess the subject for clinical complications before performing the necessary heel prick blood draw.

• A transcutaneous measurement of bilirubin and a heel stick will be performed on the neonate by a trained study nurse or clinician.
• One drop of blood will be collected on the sample card and immediately used for analysis. BiliSpec will be operated by a trained nurse or trained research assistant.
• Another drop of blood, collected in a capillary tube, will be centrifuged and then measured using the laboratory spectrophotometric bilirubinometer (Reichert UNISTAT® Bilirubinometer 1310310C). The spectrophotometric bilirubinometer will be operated by trained research assistants from the Rice department of bioengineering and the University of Malawi. Bilirubin concentration values measured by the gold standard laboratory bilirubinometer will be used to guide diagnosis.

Measurements will be made at multiple time points as indicated clinically.

The neonatal bilirubin concentration in mg/dL will be determined using the BiliSpec device, the gold standard laboratory spectrophotometric bilirubinometer, and the transcutaneous bilirubinometer described in the testing procedure. Measurements of bilirubin levels will be compared. All data will be recorded using a pre-determined data collection form. Analysis of the usability and robustness of BiliSpec will also be performed with regards to usability and device function by maintaining a log of any user error in using the device and a log of any observed device malfunctions. Data will also be collected on the effectiveness of BiliSpec to monitor neonates undergoing phototherapy.

Personal identifiers will be removed and confidentiality of the subjects will be strictly preserved. The data will be kept on a secure server accessible only to the study personnel.

• Study Type: Observational
• Enrollment (Estimated): 1000

Contacts and Locations

• Study Contact: Name: Rebecca Massey, MPH, BSN, RN; Phone Number: 713-348-6574; Email: rebecca.elias@rice.edu
• Study Contact Backup: Name: Meaghan Bond, PhD; Email: meaghan.mc.bond@rice.edu

Study Locations

• Malawi
  • Blantyre, Malawi
    • Recruiting
    • Queen Elizabeth Central Hospital
    • Contact: Queen Dube, MD; Phone Number: +265999981454; Email: drdubefirst@yahoo.com
    • Contact: Dube
  • Lilongwe, Malawi, 30700
    • Recruiting
    • Kamuzu Central Hospital
    • Contact: Msandeni Chiume, MD; Phone Number: +265995674740; Email: msandeni@gmail.com
• United States
  • Texas
    • Houston, Texas, United States, 77030
      • Active, not recruiting
      • Rice University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 1 second to 4 weeks (Child)
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Patients currently being treated at Queen Elizabeth Central Hospital or Kamuzu Central Hospital in the neonatal ward, who are less than 28 days old (neonate), and deemed to be at risk for jaundice or the patient is undergoing blue light phototherapy for treatment of jaundice.

Description

Inclusion Criteria:

• The patient is currently being treated at Queen Elizabeth Central Hospital or Kamuzu Central Hospital in the neonatal ward.
• The patient is less than 28 days old (neonate).
• The patient is deemed to be at risk for jaundice or the patient is undergoing blue light phototherapy for treatment of jaundice.
• The patient's parent or guardian has provided informed consent for their child to participate.

Exclusion Criteria:

• Parent or guardian is unable or unwilling to provide informed consent.
• The patient is unable to receive a blood draw/heel stick as determined by their clinician.

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
Quantitative Measurement of Bilirubin; Bilirubin content of the neonate will be measured by the following: BiliSpec, laboratory spectophotometric bilirubinometer (Reichert UNISTAT), and transcutaneous bilirubinometer. The infant may or may not be receiving phototherapy treatment at the time of sample measurement.	Diagnostic test: BiliSpec; BiliSpec will quantitatively measure the bilirubin content of a neonatal blood sample.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Device Accuracy	Bilirubin content measured by the BiliSpec device compared against the Reichert UNISTAT laboratory spectophotometric bilirubinometer as well as a transcutaneous bilirubinometer.	Total duration of hospital stay while inclusion criteria are met (<10 minutes per sample)

Collaborators and Investigators

• Sponsor: William Marsh Rice University
• Collaborators: Kamuzu University of Health Sciences; Lagos University Teaching Hospital (LUTH)
• Investigators: Principal Investigator: Rebecca Richards-Kortum, PhD, William Marsh Rice University; Principal Investigator: Queen Dube, MD, Kamuzu University of Health Sciences; Principal Investigator: Maria Oden, PhD, William Marsh Rice University; Principal Investigator: Msandeni Chiume, MD, Kamuzu University of Health Sciences

Publications and helpful links

General Publications

• Keahey PA, Simeral ML, Schroder KJ, Bond MM, Mtenthaonnga PJ, Miros RH, Dube Q, Richards-Kortum RR. Point-of-care device to diagnose and monitor neonatal jaundice in low-resource settings. Proc Natl Acad Sci U S A. 2017 Dec 19;114(51):E10965-E10971. doi: 10.1073/pnas.1714020114. Epub 2017 Dec 4.
• Shapiro A, Anderson J, Mtenthaonga P, Kumwenda W, Bond M, Schwarz R, Carns J, Johnston R, Dube Q, Chiume M, Richards-Kortum R. Evaluation of a Point-of-Care Test for Bilirubin in Malawi. Pediatrics. 2022 Aug 1;150(2):e2021053928. doi: 10.1542/peds.2021-053928.

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2019
• Primary Completion (Estimated): August 31, 2024
• Study Completion (Estimated): August 31, 2024

Study Registration Dates

• First Submitted: March 5, 2019
• First Submitted That Met QC Criteria: March 5, 2019
• First Posted (Actual): March 7, 2019

Study Record Updates

• Last Update Posted (Actual): June 7, 2024
• Last Update Submitted That Met QC Criteria: June 6, 2024
• Last Verified: June 1, 2024

More Information

Terms related to this study

• Keywords: Diagnostic; Point-of-Care; Low-Resource Setting
• Additional Relevant MeSH Terms: Pathologic Processes; Infant, Newborn, Diseases; Skin Manifestations; Jaundice; Hyperbilirubinemia; Hyperbilirubinemia, Neonatal; Jaundice, Neonatal
• Other Study ID Numbers: BiliSpec-COMREC

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified individual participant data for all primary outcome measures will be made available.
• IPD Sharing Time Frame: Data will be available within 6 months of study completion.
• IPD Sharing Access Criteria: Data access requests will be reviewed by an external Independent Review Panel. Requestors will be required to sign a Data Access Agreement.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ICF

Drug and device information, study documents

• 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.: Yes