Efficacy of Chloroquine + Sulfadoxine Pyrimethamine Versus Artemether + Lumefantrine for the Treatment of Uncomplicated Plasmodium Falciparum Malaria in the Philippines

The purpose of this study is to determine whether artemether + lumefantrine is as effective as chloroquine + sulfadoxine pyrimethamine in the treatment of uncomplicated Plasmodium falciparum malaria

Study Overview

• Status: Completed
• Conditions: Malaria
• Intervention / Treatment: Drug: artemether/lumafantrine vs chloroquine/sulfadoxine-pyrimethamine

Detailed Description

Background: In the Philippines, close to 11 million people in 65 provinces are at risk for acquiring malaria infections. It is still one of the ten leading causes of morbidity nationwide. Each day, roughly 150-200 people fall ill with malaria. In the past 40 years, the mortality rate stabilized at around 2/100,000 population. Of those people who have malaria, approximately 1% die per year. Malaria remains one of the major causes of death in provinces such as Palawan, Isabela, Tawi-tawi, Sulu and Butuan City. Approximately 70% of all malaria in the Philippines is Plasmodium falciparum with the remaining species being P. vivax.

Recently the Department of Health (DOH) instituted a change in the national antimalarial drug guidelines changing from using chloroquine (CQ) and sulfadoxine pyrimethamine (SP) monotherapy as first and second line drugs, respectively, to a combined chloroquine plus sulfadoxine-pyrimethamine as first-line treatment, and artemether-lumefantrine (Coartem) as second line treatment. This change was made due to increasing levels of drug resistance to the previous first and second-line therapies. In order to have an improved understanding of the trends of antimalarial drug resistance in the Philippines, the DOH is initiating a sentinel surveillance system for monitoring of antimalarial drug resistance. Three sites have been selected to be representative of the country.

Objective: To establish a sentinel surveillance system to assess the efficacy of chloroquine plus sulfadoxine-pyrimethamine versus artemether + lumefantrine for the treatment of uncomplicated P. falciparum infections in three areas of the Republic of the Philippines.

Methods: An in vivo antimalarial drug efficacy trial will be conducted in three areas of the Philippines. Subjects > 6 months of age with parasitologically confirmed, uncomplicated P. falciparum infections will be recruited. Patients will be treated with single dose SP (25 mg/kg of the sulfadoxine component in a single dose) plus CQ (25 mg/kg over three days) or artemether + lumefantrine (twice daily) over 3 days. Patients will be randomly assigned one of the two drugs regimens. Clinical and parasitological parameters will be monitored over a 28-day follow-up period to evaluate drug efficacy. Results from this study will be used to assist the DOH in assessing their national malaria treatment policy for P. falciparum malaria.

• Study Type: Interventional
• Enrollment (Actual): 560
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Philippines
  • Kalinga Province
    • Tabuk, Kalinga Province, Philippines
      • Kalinga Health Center
  • Mindinao
    • Davao City, Mindinao, Philippines
      • Davao Health Center
  • Palawan
    • Puerto Princesa, Palawan, Philippines
      • Palawan Health Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: ADULT; OLDER_ADULT; CHILD
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Weight > 10 kg;
2. Documented fever (axillary temperature >37.5oC) and/or a history of fever during the previous 24 hours in the absence of another obvious cause of fever (such as pneumonia, measles, otitis media);
3. Monoinfection with P. falciparum between 1,000 and 100,000 asexual parasites/µl as determined by microscopic examination of thick, or thick and thin peripheral blood smears;
4. Informed consent from the patient or parent/guardian (in the case of children),assent from child (ages 8 -17 years inclusive);
5. Willingness on the part of the patient to return to the clinic for regular check-ups during the 28-day follow-up period.

Exclusion Criteria:

1. Danger signs: unable to drink or breastfeed; vomiting (more than twice in the previous 24 hours); recent history of convulsions (one or more in the previous 24 hours); impaired consciousness; unable to sit or stand; 2. Severe Manifestations of P. falciparum malaria in adults and children (World Health Organization criteria)

1. Prostration (inability to sit unassisted [children], extreme weakness [adults])
2. Impaired consciousness (Blantyre coma scale [children], Glascow coma scale [adults])
3. Respiratory distress (sustained nasal flaring, indrawing, Kussmaul breathing)
4. Multiple convulsions (³2 convulsions/24 hour period)
5. Circulatory collapse (hypotension and poor perfusion)
6. Pulmonary edema
7. Abnormal bleeding
8. Jaundice
9. Hemoglobinuria
10. Severe anemia (Hb < 5 gm/dL)
11. Hypoglycemia (blood glucose < 2.2 mmol/L [<40 mg/dL])
12. Acidosis (bicarbonate <15 mmol/L)
13. Hyperparisitemia (level varies with endemicity)
14. Renal impairment (urine output < 12 mL/kg/24 hours) 3. Other underlying chronic or severe diseases (e.g., cardiac, renal, hepatic diseases, HIV/AIDS, malnutrition); 4. History of hypersensitivity reactions to any of the drugs being tested or used as alternative treatment: sulfonamides, chloroquine, artemisinins, artemether, lumefantrine, quinine or tetracycline/clindamycin; 4. Pregnancy (history of pregnancy or a positive urine pregnancy test); 5. Women who are breast feeding children less than 8 weeks of age. -

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: NONE

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Clinical cure

Secondary Outcome Measures

Outcome Measure
Hemoglobin levels

Collaborators and Investigators

• Sponsor: Centers for Disease Control and Prevention
• Collaborators: Department of Health, Philippines
• Investigators: Study Director: Dorin Bustos, MD, PhD, RITM, DOH, Philippines

Study record dates

Study Major Dates

• Study Start: July 1, 2003
• Primary Completion (ACTUAL): July 1, 2008
• Study Completion (ACTUAL): July 1, 2008

Study Registration Dates

• First Submitted: September 28, 2005
• First Submitted That Met QC Criteria: September 28, 2005
• First Posted (ESTIMATE): September 30, 2005

Study Record Updates

• Last Update Posted (ESTIMATE): September 11, 2012
• Last Update Submitted That Met QC Criteria: September 10, 2012
• Last Verified: September 1, 2012

More Information

Terms related to this study

• Keywords: malaria; chloroquine; Coartem; Plasmodium falciparum malaria; artemether lumafantrine; sulfadoxine pyrimethamine
• Additional Relevant MeSH Terms: Infections; Vector Borne Diseases; Parasitic Diseases; Protozoan Infections; Malaria; Malaria, Falciparum; Molecular Mechanisms of Pharmacological Action; Anti-Infective Agents; Enzyme Inhibitors; Antirheumatic Agents; Antiprotozoal Agents; Antiparasitic Agents; Antimalarials; Amebicides; Folic Acid Antagonists; Anti-Infective Agents, Urinary; Renal Agents; Chloroquine; Artemether; Pyrimethamine; Sulfadoxine; Fanasil, pyrimethamine drug combination
• Other Study ID Numbers: CDC-NCID-3913; U30/CCU317876-01