- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01921413
Clinical Performance Evaluation of Fyodor Urine Malaria Test (UMT)
Clinical Validation of Fyodor Urine Malaria Test (UMT)
Study Overview
Detailed Description
Primary Objective:
To evaluate the clinical performance (sensitivity and specificity) of Fyodor UMT for detecting Plasmodium falciparum malaria in febrile patients.
Secondary Objectives:
- To monitor time-to-clearance of the cognate parasite protein from patient urine
- To assess the potential effects of proteinuria, inflammation and anti-fever medications on Fyodor UMT performance
- To determine UMT performance when used for asymptomatic (afebrile) individuals, who may be carriers of the parasite.
Study Design:
- Randomized, multi-center clinical study
- Participants will be recruited from primary healthcare centers across four local government areas in Lagos State, and two schistosomiasis communities in Abeokuta-North Local Government Area of Ogun State, both in southwest Nigeria
- 1500 participants (comprising children aged 2-14 years and adults of both genders) with fever (axillary temperature ≥37.5°C) or recent history of fever in the last 48 hours (Group 1), 250 apparently "healthy" individuals (Control, Group 2), and 50 patients with Schistosoma hematobium and Rheumatoid arthritis (Group 3), will be recruited
- Binax NOW RDT-positive patients will be treated for malaria infection with Artesunate-Amodiaquine or Dihydroartemisinin-Piperaquine Sulphate, following national treatment policy
- To assess if the UMT target antigen persists in urine after treatment, 100 treated Group 1 participants with both Binax NOW and UMT positive results will be randomly selected and followed up on days 3, 7, 14, 21, and 28, using an adaptation of the WHO (2009) Protocol for Drug Therapeutic Efficacy Assessments (http://whqlibdoc.who.int/publications/2009/9789241597531_eng.pdf)
- To test the clinical specificity of the UMT, active recruitment will include 250 individuals of both genders with asymptomatic P. falciparum malaria infection (apparently "healthy, normal control group 2), and 50 with Schistosoma haematobium infection and/or rheumatoid arthritis (Group 3) - two unrelated medical conditions known to elicit proteinuria in patients (Lehman et al., 1975; Adebajo et al., 1994; Tighe & Carson, 1997)
- Participants with elevated Rheumatoid Factor (RF+) test result (i.e. RF >60 u/mL or >1:80 liter) are associated with severe rheumatoid disease. Schistosoma haematobium infection is confirmed by microscopy with egg identification or by serology
- This 6-month study will be implemented July-December 2013, during both rainy and dry seasons when malaria transmission is high and low, respectively.
Study Area:
The study will be coordinated by The ANDI Center of Excellence for Malaria Diagnosis - an International Malaria Microscopy Training & RDT Quality Assurance Testing center, & a WHO/TDR/FIND Malaria Specimen Bank Site at the College of Medicine, The University of Lagos. It will be conducted in seven primary healthcare facilities across four local government areas in Lagos State. Lagos State is situated in the southwestern part of Nigeria, and made up of densely populated urban areas and sprawling suburban areas. Malaria transmission occurs throughout the year with periods of intense seasonal malaria transmission during the rainy season. Temperatures are usually high and water pools created during the rainy season provide breeding sites for the malaria vectors, leading to epidemic outbreaks with high morbidity rates. The state is endemic for malaria, with peak transmission between April-September.
The sampling for Schistosomiasis will be carried out in Imalodo and Abuletutu schistosomiasis communities in Abeokuta-North Local Government Area of Ogun State, also in southwest Nigeria.
Description of the Study Design:
The specific aims of the study are to determine the clinical sensitivity and specificity of the UMT, and to establish assay performance characteristics in healthy asymptomatic volunteers, compared to blood smear microscopy, and Binax NOW test (Predicate device). A total of 1,800 participants, comprising children and adults of both genders presenting with malaria-like fever symptoms, patients with unrelated medical conditions (Schistosoma hematobium infection and rheumatoid arthritis, as well as apparently "healthy" (asymptomatic) control individuals will be enrolled. Febrile patients with malaria-like symptoms will be enrolled during both the rainy and dry seasons, yielding field samples during periods of both high and low malaria transmission.
Matched urine and fingerprick blood samples will be collected and tested using the UMT, and Binax NOW and microscopy, respectively. Urine and blood testing with the UMT and Binax NOW, respectively, will be performed on-site in a blinded fashion. Each urine sample will also be tested using a urinalysis dipstick and its' physicochemical characteristics (pH, protein, sugar, specific gravity, etc) are recorded. Two thin and thick blood smear slides (prepared on the same slide) per participant will be prepared from the blood specimen. One slide will be independently read by two microscopists at the ANDI Center of Excellence for Malaria Diagnosis, an internationally reputed training and referral center for malaria microscopy. The second slide will be archived for future quality assurance purpose, and thereafter shipped to Fyodor along with the remaining urine samples. Per convention, microscopic reading of blood smears will be used as the gold standard for malaria diagnosis. Patients testing positive with Binax NOW will be treated with Artesunate-Amodiaquine or Dihydroartemisinin-Piperaquine Sulphate. No clinical decision will be made based on the UMT results alone. Nevertheless, the standard routine malaria diagnostic tests will be used to manage the patient in the facility where they present. The overall agreement of the UMT and Binax NOW to microscopy analysis will be used to establish UMT sensitivity, specificity, and substantial equivalence/non-inferiority to Binax NOW test.
UMT Test Procedure:
- Add 200 µl of the freshly collected urine into a 1.5 ml or 2 ml test tube immediately before testing
- Dip the UMT strip into the urine sample and allow sample to wick up and saturate the strip for 10 minutes
- Remove the strip from the urine specimen, and place on its foil pouch packaging
- Allow reaction to proceed for 20 minutes
- Record result as positive (POS; both Test and Control Lines appear), negative (NEG; only the Control Line appears) or invalid (INV; Control Line does not appear).
Study Quality Assurance:
This study will be conducted in accordance with good clinical practices.
- Site training: All investigators, technicians and research staff working on this UMT study will be trained and certified in the conduct of studies involving human subjects per ICH guidelines
- Site Visits: Site monitoring visits will be conducted according to the guidelines outlined in the study protocol
- Blinding of Results: Separate teams will be organized to conduct patient enrollment, laboratory (Binax NOW) testing, diagnostic microscopy, data entry, and data analysis
- Control UMT Testing: Known positive and negative control materials will be used to verify UMT performance on a daily basis
- Data Collection: Research staff will fill out all data collection forms at each visit, even if a participant has not had all of the tests completed; missed follow up visits will be documented, as appropriate, on the case report forms
- The Study Coordinator will manage field research staff and provide administrative support at study sites on a day-to-day basis
- Study Quality Assurance Coordinator is qualified by training and experience, and will monitor the conduct of the trial to ensure compliance with the approved study protocol.
This clinical study will be conducted in accordance with the study protocol as approved by the Research Grants & Experimentation Ethics Committee of the College of Medicine University of Lagos, Nigeria, the Nigerian Health Research Ethics Committee guidelines, the ICH Harmonised Tripartite Guideline for Good Clinical Practice and 45CFR46 and 21CFR50, the WHO-FIND-CDC Malaria RDT Product Testing Methods Manual (Version 3), the abbreviated or non-significant risk provision of the Investigational Device Exemptions (IDE) Regulations (21 CFR Part 812.2(b)), the Protection of Human Subjects Regulations, including Subpart B Informed Consent of Human Subjects (21 CFR Part 50), the Institutional Review Board Regulations (21 CFR Part 56); and, the Financial Disclosure by Clinical Investigators Regulations (21 CFR Part 54).
Study Type
Enrollment (Actual)
Contacts and Locations
Study Locations
-
-
Lagos
-
Idi-Araba, Lagos, Nigeria
- College of Medicine of the University of Lagos
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Sampling Method
Study Population
Description
Inclusion Criteria:
Group 1 - Febrile Patients:
- Age: two years or older
- Fever at the time of presentation (axillary temperature ≥37.5°C), or history of fever within the past 48 hours
- Subjects with concurrent illnesses not listed in the exclusion criteria will be evaluated and treated for these illnesses and included in the study
- Written informed consent obtained from the participant or parent/guardian
Group 2 - Apparently Healthy Individuals:
- Children 2 years or older, as well as adults of both genders
- Afebrile
- No history of fever within the past 48 hours
- Negative Binax NOW test confirmed by Negative blood smear for clinical malaria
Group 3 - Patients with unrelated medical conditions known to elicit proteinuria in patients:
- Children 2 years or older, as well as adults
- Afebrile
- No history of fever within the past 48 hours
- Negative Binax NOW test confirmed by Negative blood smear for clinical malaria
Exclusion Criteria:
- Pregnancy
- Patients with respiratory distress, diffuse bleeding, recent seizures, coma, inability to drink, persistent vomiting, or prostration
- Chronic use of a medication (such as trimethoprim-sulfamethoxazole for preventing AIDS-associated opportunistic infections) with known antimalarial activity
- Any condition that in the opinion of the Principal Investigator would jeopardize the safety or rights of a participant in the trial or would render the participant unable to comply with the protocol
Study Plan
How is the study designed?
Design Details
- Observational Models: Case-Control
- Time Perspectives: Prospective
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Accuracy of the UMT for Clinical Malaria Diagnosis
Time Frame: Acute (day 0) fever suspected of being malaria or recent history of fever in the past 48 hours
|
• Establish sensitivity and specificity of the UMT for malaria diagnosis in febrile patients.
|
Acute (day 0) fever suspected of being malaria or recent history of fever in the past 48 hours
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Monitoring the Effectiveness of Malaria Treatment by Rapid Urine Testing
Time Frame: From Day 3 of ACT administration, and followed up weekly for 28 days
|
|
From Day 3 of ACT administration, and followed up weekly for 28 days
|
Collaborators and Investigators
Sponsor
Collaborators
Investigators
- Principal Investigator: Wellington A Oyibo, PhD, ANDI Centre of Excellence for Malaria Diagnosis, International Malaria Microscopy Training & RDT QA Center, & WHO/TDR/FIND Malaria Specimen Bank Site, Department of Medical Microbiology & Parasitology, College of Medicine, University of Lagos, Nigeria
- Study Director: William (Bill) Brieger, DrPH, Johns Hopkins University, Bloomberg School of Public Health, Baltimore, Maryland, USA
- Study Director: Wendy O'Meara, PhD, Duke University School of Medicine, Durham, North Carolina, USA
- Study Director: Nnenna Ezeigwe, MBBS, FMCPH, Coordinator, National Malaria Control Program/Federal Ministry of Health, Abuja, Nigeria
- Study Director: Godwin Ntadom, MBBS, MPH, Head, Case Management, National Malaria Control Program/Federal Ministry of Health, Abuja, Nigeria
Publications and helpful links
General Publications
- Adebajo AO, Cawston TE, Hazleman BL. Rheumatoid factors in association with rheumatoid arthritis and infectious diseases in West Africans. J Rheumatol. 1994 May;21(5):968-9. No abstract available.
- Tighe H, Warnatz K, Brinson D, Corr M, Weigle WO, Baird SM, Carson DA. Peripheral deletion of rheumatoid factor B cells after abortive activation by IgG. Proc Natl Acad Sci U S A. 1997 Jan 21;94(2):646-51. doi: 10.1073/pnas.94.2.646.
- Lehman JS Jr, Mott KE, De Souza CA, Leboreiro O, Muniz TM. The association of Schistosomiasis mansoni and proteinuria in an endemic area. A preliminary report. Am J Trop Med Hyg. 1975 Jul;24(4):616-8. doi: 10.4269/ajtmh.1975.24.616.
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Estimate)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
Other Study ID Numbers
- UMT Evaluation
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
Clinical Trials on Malaria
-
University of California, San FranciscoCenters for Disease Control and Prevention; University of Massachusetts, Amherst and other collaboratorsRecruitingPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaLao People's Democratic Republic
-
Medicines for Malaria VentureAsociacion Civil Selva AmazonicaCompletedPlasmodium Falciparum Malaria | Plasmodium Vivax MalariaPeru
-
Menzies School of Health ResearchInternational Centre for Diarrhoeal Disease Research, Bangladesh; Addis Ababa... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaEthiopia, Bangladesh, Indonesia
-
University of OxfordWellcome Trust; Ministry of public Health AfghanistanCompletedVivax Malaria | Uncomplicated Falciparum MalariaAfghanistan
-
Gadjah Mada UniversityMenzies School of Health Research; Eijkman Institute for Molecular Biology; Timika...Completed
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
London School of Hygiene and Tropical MedicineWorld Health Organization; United Nations High Commissioner for Refugees; HealthNet... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaPakistan
-
Menzies School of Health ResearchNational Health and Medical Research Council, Australia; Wellcome Trust; National...CompletedVivax Malaria | Falciparum MalariaIndonesia
-
University of IbadanShin Poong Pharm Co Ltd 161 yoksam-ro, Gangnam-Gu Seoul 135-925, Korea; Institute...CompletedPlasmodium Falciparum Malaria | Uncomplicated Malaria | Malaria FeverNigeria
-
Research Institute for Tropical Medicine, PhilippinesWorld Health OrganizationCompletedTES of Artemether-lumefantrine for Pf and Chloroquine for Pv in the Philippines From 2013-2014 (TES)Malaria | Vivax Malaria | Falciparum Malaria | Malaria Recrudescence
Clinical Trials on Urine Malaria Test
-
Foundation for Innovative New Diagnostics, SwitzerlandNational Institute of Malaria Research, New Delhi, IndiaCompleted
-
Centro de Investigação em Saúde de ManhiçaUniversity of California, San Francisco; Barcelona Institute for Global Health and other collaboratorsRecruitingMalaria | Malaria in Pregnancy | Malaria,FalciparumMozambique
-
London School of Hygiene and Tropical MedicineKilimanjaro Christian Medical Centre, TanzaniaCompletedMalaria | Febrile IllnessTanzania
-
Assistance Publique - Hôpitaux de ParisCompleted
-
Institute of Tropical Medicine, BelgiumWithdrawn
-
DBL -Institute for Health Research and DevelopmentLondon School of Hygiene and Tropical Medicine; Ministry of Health, Uganda; Artemisinin-based...Completed
-
Chinese University of Hong KongRecruitingCommunity-acquired PneumoniaHong Kong
-
University of Cape TownUniversity of Zimbabwe; University of Zambia; NIMR - Mbeya Medical Research ProgrammeCompletedTuberculosisZambia, Zimbabwe, South Africa, Tanzania
-
Centro per le Malattie TropicaliInstitute of Tropical Medicine, BelgiumCompleted
-
Pacific Edge LimitedRecruitingUrothelial CarcinomaUnited States