Evaluate Azithromycin Plus Chloroquine And Sulfadoxine Plus Pyrimethamine Combinations For Intermittent Preventive Treatment Of Falciparum Malaria Infection In Pregnant Women In Africa

• Drug: Azithromycin plus chloroquine
  
  combination tablet of 250mg azithromycin/155 chloroquine, Once daily PO for three days per treatment. There are total 3 treatments at 4-8 weeks intervals. The first treatment course will be administered during the second trimester (14-26 weeks of gestation as confirmed by ultrasound). The last treatment course should be given to subjects prior to or during 36 weeks of gestation.
• Drug: sulfadoxine-pyrimethamine
  
  Fansidar tablet (500 mg sulfadoxine /25 mg pyrimethamine), once daily, PO, single dose per treatment. There are total 3 treatments at 4-8 weeks intervals. The first treatment course will be administered during the second trimester (14-26 weeks of gestation as confirmed by ultrasound). The last treatment course should be given to subjects prior to or during 36 weeks of gestation.
  Other Name: Fansidar

• Experimental: AZCQ
  
  Azithromycin/chloroquine
  Intervention: Drug: Azithromycin plus chloroquine
• Active Comparator: SP
  
  sulfadoxine-pyrimethamine (Fansidar)
  Intervention: Drug: sulfadoxine-pyrimethamine

• 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.
• 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.

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.

• London School of Hygiene and Tropical Medicine
• Medicines for Malaria Venture