Clinical trial NCT01103063: Evaluate Azithromycin Plus Chloroquine And Sulfadoxine Plus Pyrimethamine Combinations For Intermittent Preventive Treatment Of Falciparum Malaria Infection In Pregnant Women In Africa
Official title: A Phase 3, Open Label, Randomized, Comparative Study To Evaluate Azithromycin Plus Chloroquine And Sulfadoxine Plus Pyrimethamine Combinations For Intermittent Preventive Treatment Of Falciparum Malaria Infection In Pregnant Women In Africa
Study type: INTERVENTIONAL
Overall status: TERMINATED
Phase: PHASE3
Conditions: Intermittent Preventive Treatment In Pregnancy (IPTp)
Keywords: P. falciparum malaria
IPTp
Lead sponsor: Pfizer
Sponsor class: INDUSTRY
Collaborators: name: London School of Hygiene and Tropical Medicine
name: Medicines for Malaria Venture
First posted: 2010-04-13
Enrollment: 2891
Sex: FEMALE
Minimum age (years): 16
Maximum age (years): 35
Standard ages: CHILD
ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: PREVENTION

Brief summary: The primary objective is to establish superiority of AZCQ over SP in protective efficacy for IPTp as measured by the proportion of subjects with sub-optimal pregnancy outcome.

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:

* Pregnant women (all gravidae) with ≥14 and ≤26 weeks of gestational age (by ultrasound).
* Evidence of a personally signed and dated informed consent/assent document. Assent will be obtained from subjects \<18 years of age.
* Subjects who are willing to and able to comply with scheduled visits, treatment plan, laboratory tests, and other study procedures.
* Subjects who are available for follow up at delivery and on 28 days post delivery.

Exclusion Criteria:

* Age \<16 years old or \>35 years old.
* Multiple gestations as per the ultrasound at screening.
* Clinical symptoms of malaria.
* Hemoglobin \< 8 g/dL (at enrollment).
* Any condition requiring hospitalization at enrollment.
* History of convulsions, hypertension, diabetes or any other chronic illness that may adversely affect fetal growth and viability.
* Inability to tolerate oral treatment in tablet form.
* Known allergy to the study drugs (azithromycin, chloroquine, and sulfadoxine-pyrimethamine) or to any macrolides or sulphonamides.
* Requirement to use medication during the study that might interfere with the evaluation of the study drug eg, trimethoprim-sulfamethoxazole use in subjects positive for HIV infection.
* Other severe acute or chronic medical or psychiatric condition or laboratory abnormality that may increase the risk associated with study participation.
* 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 Participants With Sub-optimal Pregnancy Outcome in Intent-to-Treat (IIT) Population
timeFrame: Approximately 40 weeks of gestational age
Secondary outcomes:
measure: Percentage of Participants With Sub-optimal Pregnancy Outcome in Efficacy Analyzable Per Protocol (PP) Population
timeFrame: Approximately 40 weeks of gestational age
measure: Percentage of Neonates With LBW (<2500 g) in ITT Population
timeFrame: Approximately 40 weeks of gestational age
measure: Percentage of Neonates With LBW (<2500 g) in Efficacy Analyzable PP Population
timeFrame: Approximately 40 weeks of gestational age
measure: Percentage of Participants With Severe Maternal Anemia (Hemoglobin [Hb] <8 g/dL) at 36-38 Weeks of Gestation
timeFrame: At 36-38 weeks of gestation.
measure: Percentage of Participants With Maternal Anemia (Hb <11 g/dL) at 36-38 Weeks of Gestation
timeFrame: At 36-38 weeks of gestation.
measure: Percentage of Participants With Placental Parasitemia at Delivery
timeFrame: Approximately 40 weeks of gestational age
measure: Percentage of Participants With Placental Malaria at Delivery Based on Histology
timeFrame: Approximately 40 weeks of gestational age
measure: Sexually Transmitted Infection (STI) Episodes Per Participant
timeFrame: Approximately 40 weeks of gestational age .
measure: Percentage of Participants With Sub-optimal Pregnancy Outcome Including Neonatal Death and Congenital Malformation
timeFrame: Approximately 40 weeks of gestational age.
measure: Change From Baseline to 36-38 Weeks of Gestation in Hb Concentration.
timeFrame: Baseline, at 36-38 weeks of gestation.
measure: Percentage of Neonates With Congenital Abnormalities at Birth
timeFrame: Approximately 40 weeks of gestational age.
measure: Percentage of Perinatal or Neonatal Deaths
timeFrame: Day 28 after delivery.
measure: Birth Weight of Live Borne Neonate
timeFrame: Approximately 40 weeks of gestational age.
measure: Number of Episodes of Symptomatic Malaria Per Participant From First Intermittent Preventive Treatment of Falciparum Dose to Delivery
timeFrame: Approximately 40 weeks of gestational age
measure: Percentage of Participants Requiring Additional Treatment for Symptomatic Malaria From First Dose to Delivery
timeFrame: Approximately 40 weeks of gestational age
measure: Percentage of Participants With Peripheral Parasitemia at 36-38 Weeks of Gestation
timeFrame: At 36-38 weeks of gestation
measure: Percentage of Participants With Peripheral Parasitemia at Delivery
timeFrame: Approximately 40 weeks of gestational age
measure: Percentage of Participants With Cord Blood Parasitemia at Delivery
timeFrame: Approximately 40 weeks of gestational age
measure: Percentage of Participants With Sexually Transmitted Infections From First Dose to 36-38 Weeks of Gestation
timeFrame: Upto 36-38 weeks of gestation
measure: Percentage of Participants With Chlamydia Trachomatis Infection at 36-38 Weeks of Gestation
timeFrame: At 36-38 weeks of gestation
measure: Percentage of Participants With Neisseria Gonorrhoeae Infection at 36-38 Weeks of Gestation
timeFrame: At 36-38 weeks of gestation
measure: Percentage of Participants With Treponema Pallidum Infection at 36-38 Weeks of Gestation
timeFrame: At 36-38 weeks of gestation
measure: Percentage of Participants With Trichomonas Vaginalis Infection at 36-38 Weeks of Gestation
timeFrame: At 36-38 weeks of gestation
measure: Percentage of Participants With Bacterial Vaginosis Infection at 36-38 Weeks of Gestation.
timeFrame: At 36-38 weeks of gestation
measure: Percentage of Neonates With Ophthalmia Neonatorum at Birth Period
timeFrame: Approximately 40 weeks of gestational age
measure: Percentage of Participants With Bacterial Infections Including Pneumonia and Other Lower Respiratory Tract Infections From First Dose to Delivery
timeFrame: Up to approximately 40 weeks of gestational age
measure: Percentage of Participants With Pre-eclampsia From Week 20 to Delivery
timeFrame: From Week 20 to approximately 40 weeks of gestational age
measure: Nasopharyngeal Swabs Positive for Macrolide Resistant Streptococcus Pneumoniae
timeFrame: Visits 6 and 7
measure: Nasopharyngeal Swabs Positive for Penicillin Resistant Streptococcus Pneumoniae
timeFrame: Visits 6 and 7
Other outcomes:
Locations:
city: Cotonou
country: Benin
facility: Centre de Santé 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: Bugando Medical Centre
city: Mwanza
country: Tanzania
facility: Nyamagana District Hospital, c/o National Institute for Medical Research, Mwanza Centre
city: Mwanza
country: Tanzania
facility: Nyamagana District Hospital
city: Kampala
country: Uganda
facility: Mulago Hospital Complex
Study officials:
affiliation: Pfizer
name: Pfizer CT.gov Call Center
role: STUDY_DIRECTOR
References:
citation: Mtove G, Kimani J, Kisinza W, Makenga G, Mangesho P, Duparc S, Nakalembe M, Phiri KS, Orrico R, Rojo R, Vandenbroucke P. Multiple-level stakeholder engagement in malaria clinical trials: addressing the challenges of conducting clinical research in resource-limited settings. Trials. 2018 Mar 22;19(1):190. doi: 10.1186/s13063-018-2563-1.
citation: Kimani J, Phiri K, Kamiza S, Duparc S, Ayoub A, Rojo R, Robbins J, Orrico R, Vandenbroucke P. Efficacy and Safety of Azithromycin-Chloroquine versus Sulfadoxine-Pyrimethamine for Intermittent Preventive Treatment of Plasmodium falciparum Malaria Infection in Pregnant Women in Africa: An Open-Label, Randomized Trial. PLoS One. 2016 Jun 21;11(6):e0157045. doi: 10.1371/journal.pone.0157045. eCollection 2016.