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

This study has been terminated.
(See termination reason in detailed description.)
Sponsor:
Collaborators:
London School of Hygiene and Tropical Medicine
Medicines for Malaria Venture
Information provided by (Responsible Party):
Pfizer
ClinicalTrials.gov Identifier:
NCT01103063
First received: April 7, 2010
Last updated: February 24, 2014
Last verified: February 2014
  Purpose

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.


Condition Intervention Phase
Intermittent Preventive Treatment In Pregnancy (IPTp)
Drug: Azithromycin plus chloroquine
Drug: sulfadoxine-pyrimethamine
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Open Label
Primary Purpose: Prevention
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

Resource links provided by NLM:


Further study details as provided by Pfizer:

Primary Outcome Measures:
  • Subjects with sub-optimal pregnancy outcome [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]

Secondary Outcome Measures:
  • Occurrence at birth of a LBW live neonate [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
  • Occurrence of severe maternal anemia (Hb <8 g/dL) [ Time Frame: at 36-38 weeks of gestational age ] [ Designated as safety issue: No ]
  • Occurrence of anemia (Hb <11 g/dL) [ Time Frame: at 36-38 weeks of gestational age ] [ Designated as safety issue: No ]
  • Occurrence of placental parasitemia [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
  • Occurrence of placental malaria as determined by histology [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
  • Number of episodes of STIs per subject including T. pallidum, N. gonorrhoeae, C. trachomatis, during the study period (diagnosis based on clinical presentation and/or on laboratory test results between Weeks 36-38). [ Time Frame: up to approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
  • Occurrence at birth of a neonates with congenital abnormalities [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
  • Occurrence of a perinatal or neonatal death [ Time Frame: Day 28 after delivery ] [ Designated as safety issue: No ]
  • Birth weight of the live-borne neonate (singleton); [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
  • Number of episodes of symptomatic malaria per subject anytime from first IPTp dose administration to delivery [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
  • Occurrence of a subject requiring additional treatment for symptomatic malaria during the study period following the first dose (diagnosed based on clinical presentation and/or lab test results) [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
  • Occurrence of peripheral parasitemia [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
  • Occurrence of peripheral parasitemia [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
  • Occurrence of cord blood parasitemia [ Time Frame: approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
  • Occurrence of STIs including T. pallidum, N. gonorrhoeae, C. trachomatis during the study period following first dose (diagnosed based on clinical presentation prior to Week 36-38 and/or lab test results between Week 36-38 of gestation) [ Time Frame: up to approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
  • Occurrence of a positive result for C. trachomatis infection (diagnosed based on lab result) [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
  • Occurrence of a positive result for N. gonorrhoeae infection (diagnosed based on lab result) [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
  • Occurrence of a positive result for T. pallidum test (diagnosed based on lab result) [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
  • Occurrence of a T. vaginalis infection (diagnosed based on lab result); [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
  • Occurrence of bacterial vaginosis (diagnosed based on lab result); [ Time Frame: at 36-38 weeks of gestation ] [ Designated as safety issue: No ]
  • Occurrence of ophthalmia neonatorum (diagnosed based on lab test results) in the neonate; [ Time Frame: up to approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
  • Occurrence of bacterial infections including pneumonia and other lower respiratory tract infections anytime from first IPTp dose administration to delivery; [ Time Frame: up to approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
  • Occurrence of pre-eclampsia from Week 20 to delivery; [ Time Frame: Wk 20 to approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
  • Occurrence of nasopharyngeal swabs positive for macrolide resistant and penicillin resistant Streptococcus pneumoniae. This test will be done in about 600 subjects each from the AZCQ and SP arms from two or more sites. [ Time Frame: baseline, Day 28 (window Day 28 - Day 42) post delivery, and about 6 mos following last IPTp course ] [ Designated as safety issue: No ]

Enrollment: 2953
Study Start Date: October 2010
Study Completion Date: November 2013
Primary Completion Date: August 2013 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: AZCQ
Azithromycin/chloroquine
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.
Active Comparator: SP
sulfadoxine-pyrimethamine (Fansidar)
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

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

Ages Eligible for Study:   16 Years to 35 Years
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01103063

Locations
Benin
Hôpital Bethesda
Cotonou, Benin
Comité National d'Éthique pour la Recherche en Santé
Cotonou, Benin
Centre de Santé d'AHOUANSORI-AGUE
Cotonou, Benin
Kenya
Siaya District Hospital
Siaya, Kenya
Malawi
Zomba Central Hospital
Zomba, Malawi
Tanzania
Teule Hospital
Muheza, Tanga, Tanzania
National Institute for Medical Research NIMR Mwanza Centre/ Nyamagana District Hospital
Mwanza, Tanzania
Bugando Medical Centre
Mwanza, Tanzania, 1903
Nyamagana District Hospital
Mwanza, Tanzania
Uganda
Mulago Hospital Complex
Kampala, Uganda
Sponsors and Collaborators
Pfizer
London School of Hygiene and Tropical Medicine
Medicines for Malaria Venture
Investigators
Study Director: Pfizer CT.gov Call Center Pfizer
  More Information

Additional Information:
No publications provided

Responsible Party: Pfizer
ClinicalTrials.gov Identifier: NCT01103063     History of Changes
Other Study ID Numbers: A0661158
Study First Received: April 7, 2010
Last Updated: February 24, 2014
Health Authority: United States: Independent Data Monitoring Committee (IDMC)

Keywords provided by Pfizer:
P. falciparum malaria
IPTp

Additional relevant MeSH terms:
Malaria
Malaria, Falciparum
Protozoan Infections
Parasitic Diseases
Chloroquine
Chloroquine diphosphate
Pyrimethamine
Sulfadoxine
Sulfadoxine-pyrimethamine
Azithromycin
Amebicides
Antiprotozoal Agents
Antiparasitic Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Antimalarials
Antirheumatic Agents
Anti-Inflammatory Agents, Non-Steroidal
Analgesics, Non-Narcotic
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Anti-Inflammatory Agents
Filaricides
Antinematodal Agents
Anthelmintics
Central Nervous System Agents
Folic Acid Antagonists

ClinicalTrials.gov processed this record on July 20, 2014