Evaluate Parasitological Clearance Rates And Pharmacokinetics Of The Combination Of Azithromycin And Chloroquine In Asymptomatic Pregnant Women With Falciparum Parasitemia In Africa

Study Overview
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Brief Summary
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The study will be conducted in asymptomatic pregnant women with P. falciparum parasitemia. The subjects will be given 3 day dosing regiment of the fixed-dose combination of Azithromycin and Chloroquine. Parasitological clearance rate with polymerase chain reaction data will be evaluated on Day 28 as primary endpoint.

Detailed Description
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After interim analysis of efficacy data by an External Data Monitoring Committee, this study was terminated. Investigators were notified on 22 Aug 2013. There were no safety concerns that led to this termination.

Official Title
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An Open Label, Non-comparative Study To Evaluate Parasitological Clearance Rates And Pharmacokinetics Of Azithromycin And Chloroquine Following Administration Of A Fixed Dose Combination Of Azithromycin And Chloroquine (Azcq) In Asymptomatic Pregnant Women With Plasmodium Falciparum Parasitemia In Sub-saharan Africa

Conditions
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Asymptomatic Parasitemia In Pregnancy

Intervention / Treatment
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* Drug: Azithromycin plus chloroquine


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Primigravidae and secundigravidae pregnant women at >=14 and <=30 weeks of gestational age (confirmed by ultrasound examination). Evidence of asymptomatic parasitemia with Plasmodium falciparum monoinfection (confirmed by microscopy) with parasite counts in the range of 80 100,000/uL on thick blood smears. Evidence of a personally signed and dated informed consent document indicating that the subject (or a legally acceptable representative if a subject is <18 years of age) has been informed of all pertinent aspects of the study and that all questions by the subject have been sufficiently answered. Assent will be obtained from subjects <18 years of age. Subjects who are willing and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures. Exclusion Criteria: Age <16 years old or >35 years old. Multiple gestations (more than one fetus) as per the ultrasound results at screening. Clinical symptoms of malaria. Hemoglobin <8 g/dL (measured at baseline). Any condition requiring hospitalization or evidence of severe concomitant infection at time of presentation. Use of antimalarial drugs in previous 4 weeks. History of convulsions, hypertension, diabetes or any other chronic illness that may adversely affect fetal growth and viability. Known allergy to the study drugs (AZ, CQ, and SP) or to any macrolides or sulphonamides. Requirement to use medication during the study that might interfere with the evaluation of the study drug of AZ or CQ or is contra indicated during pregnancy per package inserts. Severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation or investigational product administration or may interfere with the interpretation of study results and, in the judgment of the investigator, would make the subject inappropriate for entry into this study. Evidence of current obstetric complications that may adversely impact the pregnancy and/or fetal outcomes, including presence of congenital anomalies, placenta previa or abruption. Known severe sickle cell (SS) disease or sickle hemoglobin C (SC) anemia. Known family history of prolonged QT syndrome, serious ventricular arrhythmia, or sudden cardiac death.

Ages Eligible for Study
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Minimum Age: 16 Years
Maximum Age: 35 Years

Sexes Eligible for Study
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Female

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Non-Randomized
Intervention Model: Single Group Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: AZCQ<br>Azithromycin/Chloroquine | Drug: Azithromycin plus chloroquine<br>* Study drug is a fixed dose tablet of AZCQ containing 250 mg AZ and 155 mg CQ base. All subjects will be administered a 3 day course of AZCQ IPTp regimen: a single dose of 1000 mg AZ/620 mg CQ base (4 fixed dose combination tablets of AZCQ: 250mg/155mg) administered per os (PO, orally) once daily for 3 days (Days 0, 1, 2).<br>* Other names: Zithromax; Aralen;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Parasitologic Response (Polymerase Chain Reaction (PCR) Corrected) at Day 28 Post First Dose of Study Medication | The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR corrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR corrected) through the day of consideration, otherwise she is a parasitological failure. | Day 28 | 
| Percentage of Participants With Parasitologic Response (PCR Corrected) at Day 28 Post First Dose of Study Medication | The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR corrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR corrected) through the day of consideration, otherwise she is a parasitological failure. | Day 28 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 Post First Dose of Study Medication | The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR corrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR corrected) through the day of consideration, otherwise she is a parasitological failure. | Days 7, 14, 21, 35, and 42 | 
| Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 , Post First Dose of Study Medication | The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR corrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR corrected) through the day of consideration, otherwise she is a parasitological failure. | Days 7, 14, 21, 35, and 42 | 
| Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR corrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR corrected) through the day of consideration, otherwise she is a parasitological failure. | Days 7, 14, 21, 28, 35, and 42 | 
| Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | The proportion of participants with parasitological response was estimated from the Kaplan Meier curve based on the time to the first occurrence of parasitological failure (PCR uncorrected). A participant will be a parasitological responder if she has a zero parasite count on the Day 7 visit without subsequent recurrence (PCR uncorrected) through the day of consideration, otherwise she is a parasitological failure. | Days 7, 14, 21, 28, 35, and 42 | 
| Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication | Parasite counts (actual counts per microliter of blood) was measured at various time points. | Days 7, 14, 21, 28, 35, and 42 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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P. falciparum malaria, asymptomatic parasitemia, parasitological clearance, Intermittent Preventive Treatment of Falciparum Malaria in Pregnant Women (IPTp)