- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT01546961
Chloroquine Population Pharmacokinetics in Pre and Post-partum Women (KCP)
The Population Pharmacokinetics of Chloroquine for the Treatment of Uncomplicated P.Vivax Malaria in Pre- and Post-partum Women.
Study Overview
Detailed Description
For the treatment of P.vivax the standard treatment is chloroquine. There is a growing body of evidence suggesting that pregnant women may require different doses of drugs, including antimalarials, due to the physiological changes of pregnancy. It is important that any drug used in pregnant women is given at the correct dose. The only way to evaluate this is by pharmacokinetic studies. We propose to evaluate the pharmacokinetics of chloroquine when use to treat P.vivax in the 2nd or 3rd trimester of pregnancy. The same evaluation in the same woman post-partum is required as a control.
The two most recent pharmacokinetic publications conclude differently on chloroquine dosing in pregnant women: one suggests no dose adjustment and the other that a higher dose is probably needed. It is crucial that pregnant women are dosed correctly to maximise cure and minimize the chance for recurrence and the harmful effects of malaria. The proposed study on the pharmacokinetics of chloroquine treatment in pregnant women will solve this dilemma.
Pregnant women on the Thai-Burmese border are encouraged to attend antenatal care often for early detection and treatment of malaria. Low birth weight due to P.vivax affects primigravida and multigravida, not just primarily primigravida as with P.falciparum(highlighted in the attached reference). Hence it is important to consider these women for radical cure. This is not possible during pregnancy as primaquine is contraindicated so the next best time is in the post-partum period. During the post-partum period the woman remains in close contact with midwives for infant care and for their personal health. The midwives also have a record of malaria attacks during pregnancy.
We know more about chloroquine than any other antimalarial used in pregnancy. It has been widely used for prevention and treatment of malaria in pregnancy and in women with autoimmune disease such systemic lupus and rheumatoid arthritis high doses of hydroxychloroquine have been given daily including during the first trimester of pregnancy. Although data from prospective clinical trials of malaria are limited, this drug is considered safe in all trimester of pregnancy and in lactation.
For treatment of uncomplicated P.vivax WHO recommends chloroquine and primaquine where P.vivax remains chloroquine sensitive. A 14 day course of primaquine is recommended for radical cure of P.vivax. WHO advises not to use primaquine during pregnancy or in severe G6PD. WHO permits the use of primaquine during lactation if the breast fed infant is not G6PD deficient.
The possibility that women with recurrent P.vivax in the same pregnancy may have chloroquine resistant P.vivax needs to be considered. While the combination of chloroquine and primaquine cannot be used in pregnancy and the safety and efficacy of ACTs are still undergoing evaluation we need to explore alternatives to chloroquine for such cases. ACTs are recommended for chloroquine resistant P.vivax by WHO and one ACT considered safe in pregnancy and lactation is a 7 day course of artesunate-clindamycin.
Study Type
Enrollment (Actual)
Phase
- Not Applicable
Contacts and Locations
Study Locations
-
-
Mae Sot
-
Tak, Mae Sot, Thailand, 63110
- Shoklo Malaria Research Unit
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
Inclusion Criteria:
- Age 18-50 years
- Gestational age (ultrasound confirmed) > 13.0 weeks
- Viable fetus as assessed by ultrasound scanning
- Microscopically confirmed uncomplicated P.vivax malaria
- Willingness and ability to comply with the study protocol for the duration of the trial
- Written informed consent provided
- No signs of labour
Exclusion Criteria:
- Known hypersensitivity to chloroquine
- Clinical or laboratory features of severe malaria based on WHO criteria-Appendix 1
- Gastrointestinal dysfunction that could alter absorption or motility
- History or known liver diseases or other chronic diseases (excluding thalassaemia & G6PD deficiency)
- Presence of intercurrent illness or any condition which in the judgement of the investigator would place the patient at undue risk or interfere with the results of the study
- Splenectomy
- Hematocrit (HCT) < 20% (based on field reading i.e. capillary sample)
- Taking contraindicated medications
- History of narcotic or alcohol abuse
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Chloroquine
Chloroquine phosphate GPO® (Government Pharmaceutical Organization, Thailand) 250 mg (equivalent to chloroquine base 150 mg). Dosing will be at 0, 24, 48 hrs with 10 mg/kg on day 0 and day 1, and 5 mg/kg on day 2. |
Chloroquine phosphate GPO® (Government Pharmaceutical Organization, Thailand) 250 mg (equivalent to chloroquine base 150 mg). Dosing will be at 0, 24, 48 hrs with 10 mg/kg on day 0 and day 1, and 5 mg/kg on day 2. |
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Population Pharmacokinetics of Chloroquine
Time Frame: 63 days
|
Population pharmacokinetic parameters up to day 63 in pregnant women with uncomplicated P.vivax malaria, and in the same women post-partum with P.vivax or without P.vivax.
|
63 days
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Relationship between pharmacokinetics and symptoms
Time Frame: 63 days
|
Chloroquine pharmacokinetics versus symptomatology
|
63 days
|
Efficacy of Chloroquine
Time Frame: 63 days
|
Chloroquine efficacy against P.vivax
|
63 days
|
Reticulocyte counts
Time Frame: 63 days
|
Effect of chloroquine treatment on reticulocyte counts
|
63 days
|
Pregnancy outcomes
Time Frame: 63 days
|
Pregnancy outcomes (abortions, low birth weight, premature birth, congenital abnormality, stillbirths, neonatal and infant mortality)
|
63 days
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Rose McGready, MD, University of Oxford
Study record dates
Study Major Dates
Study Start (Actual)
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 (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
Other Study ID Numbers
- SMRU1003
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 Vivax 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
-
University of OxfordMenzies School of Health ResearchCompletedUncomplicated Vivax MalariaAfghanistan, Ethiopia, Indonesia, Vietnam
-
Centers for Disease Control and PreventionTerminated
-
Menzies School of Health ResearchMinistry of Health, MalaysiaUnknownPlasmodium Vivax Malaria Without ComplicationMalaysia
-
Menzies School of Health ResearchInternational Centre for Diarrhoeal Disease Research, Bangladesh; Addis Ababa... and other collaboratorsCompletedMalaria | Vivax Malaria | Falciparum MalariaEthiopia, Bangladesh, Indonesia
-
Menzies School of Health ResearchAga Khan University; University of Melbourne; Universitas Sumatera Utara; Ethiopian... and other collaboratorsRecruitingVivax Malaria | Malaria, Vivax | Plasmodium Vivax | Malaria RelapseCambodia, Ethiopia, Indonesia, Pakistan
-
Menzies School of Health ResearchUniversity of Melbourne; Curtin University; Addis Ababa University; Fundação de... and other collaboratorsNot yet recruitingVivax MalariaBrazil, Ethiopia, Indonesia, Papua New Guinea
-
London School of Hygiene and Tropical MedicineHealthNet TPOCompletedMalaria | Vivax MalariaPakistan
-
London School of Hygiene and Tropical MedicineHealthNet TPOCompletedMalaria | Vivax Malaria
Clinical Trials on Chloroquine
-
Dinka DugassaEthiopian Public Health InstituteCompletedMalaria | Efficacy | Vivax Malaria | ChloroquineEthiopia
-
GlaxoSmithKlineMedicines for Malaria VentureCompletedMalaria, VivaxThailand, India, Brazil, Ethiopia, Peru, Bangladesh, Cambodia, Philippines
-
Fundação de Medicina Tropical Dr. Heitor Vieira...CompletedCOVID-19 | SARS-CoV Infection | Clinical Trial | Severe Acute Respiratory Syndrome (SARS) PneumoniaBrazil
-
HaEmek Medical Center, IsraelT MAY BIOPHARMA LTD.Terminated
-
Ministry of Health, BhutanMenzies School of Health Research; Asia Pacific Malaria Elimination NetworkUnknown
-
Tanta UniversityCompleted
-
Bandim Health ProjectCompleted
-
Maastricht Radiation OncologyNational Cancer Institute (NCI); Maastricht University Medical CenterTerminatedSmall Cell Lung CancerNetherlands
-
Bandim Health ProjectCompleted
-
PATHMahidol Oxford Tropical Medicine Research UnitTerminated