Chloroquine Population Pharmacokinetics in Pre and Post-partum Women

This study is currently recruiting participants. (see Contacts and Locations)
Verified August 2013 by University of Oxford
Sponsor:
Information provided by (Responsible Party):
University of Oxford
ClinicalTrials.gov Identifier:
NCT01546961
First received: March 1, 2012
Last updated: August 27, 2013
Last verified: August 2013
  Purpose

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 it is given at the correct dose. The only way to evaluate this is by pharmacokinetic studies. The investigators 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.


Condition Intervention
Vivax Malaria
Drug: Chloroquine

Study Type: Interventional
Study Design: Endpoint Classification: Pharmacokinetics Study
Intervention Model: Single Group Assignment
Masking: Open Label
Primary Purpose: Treatment
Official Title: The Population Pharmacokinetics of Chloroquine for the Treatment of Uncomplicated P.Vivax Malaria in Pre- and Post-partum Women.

Resource links provided by NLM:


Further study details as provided by University of Oxford:

Primary Outcome Measures:
  • Population Pharmacokinetics of Chloroquine [ Time Frame: 63 days ] [ Designated as safety issue: No ]
    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.


Secondary Outcome Measures:
  • Relationship between pharmacokinetics and symptoms [ Time Frame: 63 days ] [ Designated as safety issue: No ]
    Chloroquine pharmacokinetics versus symptomatology

  • Efficacy of Chloroquine [ Time Frame: 63 days ] [ Designated as safety issue: No ]
    Chloroquine efficacy against P.vivax

  • Reticulocyte counts [ Time Frame: 63 days ] [ Designated as safety issue: No ]
    Effect of chloroquine treatment on reticulocyte counts

  • Pregnancy outcomes [ Time Frame: 63 days ] [ Designated as safety issue: Yes ]
    Pregnancy outcomes (abortions, low birth weight, premature birth, congenital abnormality, stillbirths, neonatal and infant mortality)


Estimated Enrollment: 160
Study Start Date: December 2010
Estimated Study Completion Date: January 2014
Estimated Primary Completion Date: January 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.

Drug: 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.


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.

  Eligibility

Ages Eligible for Study:   18 Years to 50 Years
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01546961

Contacts
Contact: Rose McGready, MD +6655-545-021 rose@shoklo-unit.com

Locations
Thailand
Shoklo Malaria Research Unit Recruiting
Tak, Mae Sot, Thailand, 63110
Contact: Rose McGready, MD    +6655-545-021    rose@shoklo-unit.com   
Principal Investigator: Rose McGready, MD         
Sponsors and Collaborators
University of Oxford
Investigators
Principal Investigator: Rose McGready, MD University of Oxford
  More Information

No publications provided

Responsible Party: University of Oxford
ClinicalTrials.gov Identifier: NCT01546961     History of Changes
Other Study ID Numbers: SMRU1003
Study First Received: March 1, 2012
Last Updated: August 27, 2013
Health Authority: Thailand: Ethical Committee

Keywords provided by University of Oxford:
Chloroquine
Uncomplicated vivax malaria

Additional relevant MeSH terms:
Malaria
Malaria, Vivax
Protozoan Infections
Parasitic Diseases
Chloroquine
Chloroquine diphosphate
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Filaricides
Antinematodal Agents
Anthelmintics
Central Nervous System Agents

ClinicalTrials.gov processed this record on July 24, 2014