Chloroquine Alone or in Combination for Malaria in Children in Malawi

NCT00379821 | Completed Phase 3 Results

• 1 other identifier: 06-0022
• Study Type: interventional
• Target: 640
• Locations: 1 country
• Sites: 1

Brief Summary

Malaria is a sickness caused by a germ that can get into a person's body when a mosquito bites them. It can cause fever, headache, body aches and weakness. It can even cause death, especially in children. When malaria is treated with the appropriate medicine(s), it can be cured completely. The purpose of this study is to find out if it is better to use chloroquine alone or in combination with another drug to most effectively treat malaria. About 640 children with malaria, aged 6 months to 5 years of age, from the Blantyre Malaria Project Research Clinic at the Ndirande Health Center in Malawi will be in the study. They will be treated with either chloroquine alone or a combination of chloroquine plus another medication (azithromycin or artesunate or atovaquone-proguanil) every time they get malaria for a year. Blood samples will be collected and tested at least every 4 weeks. Participants will be involved in the study for 1 year.

Conditions

Plasmodium Falciparum Infection

Keywords

chloroquine, malaria, Plasmodium falciparum, Malawi, children

Outcome Measures

Primary Outcomes (1)

• Number of Clinical Malaria Episodes Per Year of Follow-up

  Clinical malaria episode was defined as at least one symptom of malaria and a positive malaria smear. The number of clinical malaria episodes (not including the initial malaria episode) reported by participants during follow up is presented as the number per Person Years at Risk (PYAR).

  1 year

Secondary Outcomes (37)

• Number of Participants With Day 28 Adequate Clinical and Parasitologic Response in Each Treatment Arm

  Day 28 of initial malaria episode (Episode 0)

• Number of Participants With Day 28 Adequate Clinical and Parasitologic Response in Each Treatment Arm

  Day 28 of first subsequent malaria episode (Episode 1)

• Number of Participants With Day 28 Adequate Clinical and Parasitologic Response in Each Treatment Arm

  Day 28 of second subsequent malaria episode (Episode 2)

• Number of Participants With Day 28 Adequate Clinical and Parasitologic Response in Each Treatment Arm

  Day 28 of third subsequent malaria episode (Episode 3)

• Number of Participants With Day 28 Adequate Clinical and Parasitologic Response in Each Treatment Arm

  Day 28 of fourth subsequent malaria episode (Episode 4)

Study Arms (4)

CQ Monotherapy

EXPERIMENTAL

N=160: treat with Chloroquine (CQ) alone.

Drug: Chloroquine

CQ plus atovaquone proguanil

EXPERIMENTAL

N=160: treat with CQ plus atovaquone proguanil.

Drug: Atovaquone-proguanil; Drug: Chloroquine

CQ plus artesunate

EXPERIMENTAL

N=160: treat with CQ plus artesunate.

Drug: Artesunate; Drug: Chloroquine

CQ plus azithromycin

EXPERIMENTAL

N=160: treat with CQ plus azithromycin.

Drug: Azithromycin; Drug: Chloroquine

Interventions

Atovaquone-proguanil DRUG

Atovaquone-proguanil: once a day for 3 days, Pediatric tablet: 62.5 mg/25 mg, Full strength tablet: 250 mg/100 mg

CQ plus atovaquone proguanil

Artesunate DRUG

Artesunate: 4mg/kg once a day for 3 days, 50 mg tablet

CQ plus artesunate

Azithromycin DRUG

Azithromycin 30 mg/kg once a day for 3 days, 200 mg/5cc suspension

CQ plus azithromycin

Chloroquine DRUG

Chloroquine: 10 mg/kg on days 0 and 1, 5 mg/kg/day on day 2, 100 mg tablet.

CQ Monotherapy; CQ plus artesunate; CQ plus atovaquone proguanil; CQ plus azithromycin

Eligibility Criteria

• Age: 6 Months - 5 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Subjects aged greater than or equal to 6 months to 5 years presenting to Ndirande Health Centre with signs or symptoms consistent with malaria including, but not limited to, one or more of the following:
• fever at the time of evaluation (axillary temperature greater than or equal to 37.5 degrees Celsius by digital thermometer)
• report of fever within the last two days
• clinically profound anemia (conjunctival or palmar pallor)
• headache
• body aches
• abdominal pain
• decreased intake of food or fluids
• weakness
• Weight greater than or equal to 5kg.
• Positive malaria smear for P. falciparum mono-infection with parasite density 2,000-200,000/mm\^3.
• Planning to remain in the study area for 1 year.
• Willingness to return for four-weekly routine visits, as well as unscheduled sick visits.
• Parental/guardian consent for each participant.

You may not qualify if:

• Signs of severe malaria: One or more of the following:
• hemoglobin less than or equal to 5 g/dL
• prostration
• respiratory distress
• bleeding
• recent seizures, coma or obtundation (Blantyre coma score \< 5)
• inability to drink
• persistent vomiting
• Known allergy or history of adverse reaction to chloroquine (CQ), artesunate, azithromycin, erythromycin or atovaquone-proguanil (AP)
• Chronic medication with any antibiotic or anti malarial medication
• Previous enrollment in this study
• Alanine aminotransferase (ALT) more than 5x the upper limit of normal or creatinine greater than 3x the upper limit of normal
• Evidence of chronic disease or physical stigmata of severe malnutrition (i.e., loss of muscle mass or subcutaneous tissue, edema, or skin or hair findings consistent with severe malnutrition)

Sponsors & Collaborators

• National Institute of Allergy and Infectious Diseases (NIAID): lead

Study Sites (1)

Blantyre Malaria Project - Ndirande Health Centre

Blantyre, Blantyre, Malawi

Location

Related Publications (1)

• Laufer MK, Thesing PC, Dzinjalamala FK, Nyirenda OM, Masonga R, Laurens MB, Stokes-Riner A, Taylor TE, Plowe CV. A longitudinal trial comparing chloroquine as monotherapy or in combination with artesunate, azithromycin or atovaquone-proguanil to treat malaria. PLoS One. 2012;7(8):e42284. doi: 10.1371/journal.pone.0042284. Epub 2012 Aug 17.

  PMID: 22912697 BACKGROUND

MeSH Terms

Conditions

Malaria; Malaria, Falciparum

Interventions

atovaquone, proguanil drug combination; Artesunate; Azithromycin; Chloroquine

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases

Intervention Hierarchy (Ancestors)

Artemisinins; Reactive Oxygen Species; Free Radicals; Inorganic Chemicals; Organic Chemicals; Sesquiterpenes; Terpenes; Hydrocarbons; Erythromycin; Macrolides; Polyketides; Lactones; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Results Point of Contact

• Title: Christopher Plowe, MD, MPH
• Organization: Malaria Section, Center for Vaccine Development, University of Maryland School of Medicine

cplowe@medicine.umaryland.edu

410-706-2491

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: LTE60
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: NIH
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: September 21, 2006
• First Posted: September 25, 2006
• Study Start: February 1, 2007
• Primary Completion: August 1, 2009
• Study Completion: September 1, 2012
• Last Updated: August 11, 2014
• Results First Posted: July 27, 2011

Record last verified: 2014-07

Locations

MA (1)