Clinical trial NCT01103713: Evaluate Parasitological Clearance Rates And Pharmacokinetics Of The Combination Of Azithromycin And Chloroquine In Asymptomatic Pregnant Women With Falciparum Parasitemia In Africa
Official title: 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
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Asymptomatic Parasitemia In Pregnancy
Keywords: P. falciparum malaria
asymptomatic parasitemia
parasitological clearance
Intermittent Preventive Treatment of Falciparum Malaria in Pregnant Women (IPTp)
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
First posted: 2010-04-15
Enrollment: 168
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: no
Allocation: NON_RANDOMIZED
Intervention model: SINGLE_GROUP
Primary purpose: TREATMENT

Brief summary: 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: 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.

Eligibility criteria: 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.

Primary outcomes:
measure: Percentage of Participants With Parasitologic Response (Polymerase Chain Reaction (PCR) Corrected) at Day 28 Post First Dose of Study Medication
timeFrame: Day 28
measure: Percentage of Participants With Parasitologic Response (PCR Corrected) at Day 28 Post First Dose of Study Medication
timeFrame: Day 28
Secondary outcomes:
measure: Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 Post First Dose of Study Medication
timeFrame: Days 7, 14, 21, 35, and 42
measure: Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 35, and 42 , Post First Dose of Study Medication
timeFrame: Days 7, 14, 21, 35, and 42
measure: Percentage of Participants With Parasitologic Response (PCR Corrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication
timeFrame: Days 7, 14, 21, 28, 35, and 42
measure: Percentage of Participants With Parasitologic Response (PCR Uncorrected) at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication
timeFrame: Days 7, 14, 21, 28, 35, and 42
measure: Number of Asexual P. Falciparum Per Microliter of Blood at Days 7, 14, 21, 28, 35, and 42 Post First Dose of Study Medication
timeFrame: Days 7, 14, 21, 28, 35, and 42
Other outcomes:
measure: Summary of Pregnancy Outcome: Location of Delivery
timeFrame: Following delivery or pregnancy termination
measure: Summary of Pregnancy Outcome: Mode of Delivery
timeFrame: Following delivery or pregnancy termination
measure: Summary of Pregnancy Outcome: Delivery Assisted by Trained Obstetric Personnel?
timeFrame: Following delivery or pregnancy termination
measure: Summary of Pregnancy Outcome: Labor Induced?
timeFrame: Following delivery or pregnancy termination
measure: Summary of Pregnancy Outcome: Complications During Delivery?
timeFrame: Following delivery or pregnancy termination
measure: Summary of Pregnancy Outcome: Outcome of Birth
timeFrame: Following delivery or pregnancy termination
measure: Incidence of Fever Based on Oral Temperature
timeFrame: Baseline, Days 1, 2, 7, 14, 21, 28, 35, and 42
measure: Summary of Hemoglobin Concentration: Abnormal Hemoglobin Level
timeFrame: Day 42
measure: Summary of Serum Azithromycin Concentration Versus Time
timeFrame: Planned time: 0 (Day 0), 48 (Day 2), 50 (Day 2), 56 (Day 2), 168 (Day 7), and 336 (Day 14) hours post the first dose. Note: Assuming "hour not specified" as 0 hours on Day 7 and Day 14 for planned time post first dose calculation.
measure: Summary of Plasma Chloroquine Concentration Versus Time
timeFrame: Planned time: 0 (Day 0), 48 (Day 2), 50 (Day 2), 56 (Day 2), 168 (Day 7), 336 (Day 14), 504 (Day 21) and 672 (Day 28) post first dose. Note: Assuming "hour not specified" as 0 hours on Days 7, 14, 21 and 28 for planned time post first dose calculation.
measure: Summary of Plasma Desethylchloroquine Concentration Versus Time
timeFrame: Planned time: 0 (Day 0), 48 (Day 2), 50 (Day 2), 56 (Day 2), 168 (Day 7), 336 (Day 14), 504 (Day 21) and 672 (Day 28) post first dose. Note: Assuming "hour not specified" as 0 hours on Days 7, 14, 21 and 28 for planned time post first dose calculation.
Locations:
city: Cotonou
country: Benin
facility: Centre de Sante d'AHOUANSORI -AGUE
city: Cotonou
country: Benin
facility: Hôpital Bethesda
city: Siaya
country: Kenya
facility: Siaya District Hospital
city: Zomba
country: Malawi
facility: Zomba Central Hospital
city: Muheza
country: Tanzania
facility: Teule Hospital
state: Tanga
city: Mwanza
country: Tanzania
facility: National Institute for Medical Research (Mwanza Centre)/ Nyamagana District Hospital
city: Kampala
country: Uganda
facility: Mulanda Health Centre IV
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References: