G6PD Assessment Before Primaquine for Radical Treatment of Vivax Malaria
试验速览
- 阶段
- 4 期
- 状态
- 已完成
- 入组人数
- 1,000
- 试验地点
- 1
- 主要终点
- Sensitivity of CareStart™ G6PD rapid test compared to a genotyping result as gold-standard
研究概览
简要总结
This will be a single-arm observational cohort study. Malaria patients with Plasmodium vivax and meeting study inclusion criteria, who give consent to be enrolled in the study, will have their G6PD status measured by the CareStart™ G6DP rapid diagnostic test (G6PD RDT), and primaquine prescribed according to the result. According to the G6PD RDT result, primaquine will be prescribed at 0.25mg/kg/day for 14 days (normal patients) or 0.75mg/kg weekly for eight weeks (deficient patients). All will receive treatment with chloroquine to clear asexual stages of infection.
Patients will be reviewed at day 2, day 7 and day 14. At these visits patients will undergo a brief clinical assessment and a small blood sample will be taken for repeat haemoglobin measurement and dried blood spot for carboxyprimaquine measurement (day 7 and day 14 only).
In general, antimalarial treatment will be unsupervised to reflect field conditions. However a subset of 25 G6PD normal patients at a single site will have each day of their primaquine treatment administered and observed at the treatment centre. This is to determine a calibration curve for primaquine pharmacokinetic studies.
Dried blood spots will be stored appropriately. Day zero samples will be genotyped in Bangkok (MORU, Dr. Mallika Imwong) after DNA extraction. PCR-RFLP will be used to detect the allele associated with the Mediterranean variant of G6PD deficiency. In addition DNA extracts will be sent for more systematic genetic testing for known G6PD variants through existing collaborations with the Wellcome Trust Sanger Institute. The day 7 and 14 dried blood spot samples will be analysed in the MORU pharmacology laboratory for primaquine and carboxyprimaquine concentrations, from which adherence to primaquine can be determined retrospectively, using the subset of 25 patients receiving directly observed therapy to calibrate the results.
Funder: WellcomeTrust, Grant reference: 107548/Z/15/Z
详细描述
- Screening All patients registering for outpatient services in the outpatient department will undergo routine investigation. When malaria is suspected, a thick and thin blood smear will be obtained for microscopic diagnosis of Plasmodium vivax or a malaria RDT undertaken. After the diagnosis is confirmed microscopically, an assessment will be made to see if the patient fulfils the study inclusion and exclusion criteria.
The following clinical screening procedures will be performed. The age, gender, ethnic group, and contact details of the subject will be recorded in the source documents. In the medical history, any history of chronic disease including previous history of haemolysis or anaemia will be noted along with a history of allergy to any medications (including chloroquine or primaquine).
Pregnancy is a contraindication to primaquine and all women considered at risk of pregnancy will undergo urine pregnancy testing prior to enrolment. A pregnancy test is done routinely in Afghanistan, consistent with National Treatment Guidelines.
Vital signs (axillary temperature in degrees Celsius, heart rate, respiratory rate, blood pressure, and weight in kilograms) will be recorded. The physician will perform a general systems examination. 2. Consent Patients who fulfil the study inclusion and exclusion criteria will be approached for informed consent. 3. Procedures after enrolment
Once informed consent is given, a second capillary blood sample (finger prick) will be taken for:
- CareStart RDT G6PD test. The RDT will be read at the appropriate time (10 minutes) and the result noted in the source documents. The RDT itself will be labelled and retained for future reference. It can also be analysed for host and parasite genotypes.
- Baseline haemoglobin measurement via the HemoCue system. This will generally involve use of a micropipette and the HemoCue microcuvettes.
- Collection of a dried blood spot (FTA card) labelled with an individual barcode.
- If a malaria RDT was used for diagnosis this will also be labelled and kept if possible for future analyses of G6PD and parasite genotyping.
- Biosensor recordings will also be made in a subset of patients at day 0 and day 14, if and when the device becomes available. These results will not influence patient management which will be based only on the RDT result.
- Antimalarials Chloroquine will be provided aiming for a dose of 10 mg/kg on day 0 & 1 and 5mg/kg on day 2, (Afghanistan NMLCP guidelines).
研究设计
- 研究类型
- Interventional
- 分配方式
- Non Randomized
- 干预模型
- Parallel
- 主要目的
- Diagnostic
- 盲法
- None
入排标准
- 年龄范围
- 6 Months 至 —（Child, Adult, Older Adult）
- 性别
- All
- 接受健康志愿者
- 否
入选标准
- •Adults and children >6 months
- •Confirmed diagnosis of Plasmodium vivax mono-infection
- •Ability to swallow oral medication
- •Participant (or parent/guardian if <15 years old) is willing and able to give documented informed consent and comply with study requirements
排除标准
- •Severe malaria (see World Health Organisation definition)
- •P. falciparum infection
- •Pregnancy or lactation
- •Hypersensitivity (allergy) to primaquine or chloroquine
- •Presence of any condition which in the judgement of the investigator would place the subject at undue risk or interfere with the results of the study e.g. other acute febrile conditions or chronic disease
- •Ongoing involvement in another research study
研究组 & 干预措施
G6PD Deficient
干预措施: Chloroquine (Drug)
G6PD Normal
干预措施: Chloroquine (Drug)
G6PD Normal
干预措施: Primaquine 0.25 mg/kg/day (Drug)
G6PD Deficient
干预措施: Primaquine 0.75 mg/kg weekly (Drug)
结局指标
主要结局
Sensitivity of CareStart™ G6PD rapid test compared to a genotyping result as gold-standard
时间窗: 3 years
Specificity of CareStart™ G6PD rapid test compared to a genotyping result as gold-standard
时间窗: 3 years
次要结局
- The degree to which healthcare workers act appropriately on the results of G6PD testing in terms of primaquine prescription(3 years)
- Barriers to long-term use of the approach based on a qualitative questionnaire-based survey(3 years)
- Percentage of P. vivax patients receiving a correct primaquine prescription after G6PD testing compared to using phenotype as gold standard(3 years)
- Level of primaquine metabolite in dried blood spots collected after treatment(2, 7 and 14 days)
- Level of whole blood carboxyprimaquine at day 7(7 days)
- Level of whole blood carboxyprimaquine at day 14(14 days)