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: September 10, 2014
Last verified: September 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:
  • Percentage Participants With Sub-optimal Pregnancy Outcome in Intent-to-Treat (IIT) Population [ Time Frame: Approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
    Adverse pregnancy outcomes were defined as live-borne neonate (singleton) with low birth weight (LBW) (<2,500 g), premature births (<37 weeks as confirmed by the Ballard score), abortion (≤28 weeks), still birth (>28 weeks), lost to follow-up prior to termination of pregnancy or delivery, or missing birth weight of the neonates.


Secondary Outcome Measures:
  • Percentage of Participants With Sub-optimal Pregnancy Outcome in Efficacy Analyzable Per Protocol (PP) Population [ Time Frame: Approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
    Adverse pregnancy outcomes were defined as live-borne neonate (singleton) with LBW (<2,500g), premature births (<37 weeks as confirmed by the Ballard score), abortion (≤28 weeks), still birth (>28 weeks), lost to follow-up prior to termination of pregnancy or delivery, or missing birth weight of the neonates.

  • Percentage of Neonates With LBW (<2500 g) in ITT Population [ Time Frame: Approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
    LBW was defined as live birth weight <2500 g (up to and including 2499 g).

  • Percentage of Neonates With LBW (<2500 g) in Efficacy Analyzable PP Population [ Time Frame: Approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
    LBW was defined as live birth weight <2500 g (up to and including 2499 g).

  • Percentage of Participants With Severe Maternal Anemia (Hemoglobin [Hb] <8 g/dL) at 36-38 Weeks of Gestation [ Time Frame: At 36-38 weeks of gestation. ] [ Designated as safety issue: No ]
    Severe maternal anemia was defined as Hb <8 g/dL.

  • Percentage of Participants With Maternal Anemia (Hb <11 g/dL) at 36-38 Weeks of Gestation [ Time Frame: At 36-38 weeks of gestation. ] [ Designated as safety issue: No ]
    Anemia was defined as Hb <11 g/dL.

  • Percentage of Participants With Placental Parasitemia at Delivery [ Time Frame: Approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
    Participants with placental parasitemia at delivery were diagnosed using Placental blood smear at birth from participants who deliver at hospital.

  • Percentage of Participants With Placental Malaria at Delivery Based on Histology [ Time Frame: Approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
    Participants positive for placental malaria at delivery were evaluated based on placental histology.

  • Sexually Transmitted Infection (STI) Episodes Per Participant [ Time Frame: Approximately 40 weeks of gestational age . ] [ Designated as safety issue: No ]
    Number of episodes of sexually transmitted infection episodes per participant were noted. The STI's including Treponema pallidum, Neisseria gonorrhoeae, Chlamydia trachomatis, from first dose to delivery (diagnosis was based on clinical presentation and lab results).

  • Percentage of Participants With Sub-optimal Pregnancy Outcome Including Neonatal Death and Congenital Malformation [ Time Frame: Approximately 40 weeks of gestational age. ] [ Designated as safety issue: No ]
    Sub-optimal pregnancy outcome including neonatal deaths and congenital malformations, defined as any of the following: live-borne neonate (singleton) with low birth-weight (or LBW for short, defined as live birth weight <2,500g), premature birth (<37 weeks), abortion (≤28 weeks), still birth (>28 weeks), neonatal death, congenital malformation, lost to follow-up prior to termination of pregnancy or delivery, or missing birth weight of the neonates.

  • Change From Baseline to 36-38 Weeks of Gestation in Hb Concentration. [ Time Frame: Baseline, at 36-38 weeks of gestation. ] [ Designated as safety issue: No ]
    Change from Baseline to 36-38 weeks of gestation in Hb concentration was noted.

  • Percentage of Neonates With Congenital Abnormalities at Birth [ Time Frame: Approximately 40 weeks of gestational age. ] [ Designated as safety issue: No ]
    Neonates with congenital abnormalities at birth were noted.

  • Percentage of Perinatal or Neonatal Deaths [ Time Frame: Day 28 after delivery. ] [ Designated as safety issue: No ]
    Percentage of perinatal or neonatal deaths were noted.

  • Birth Weight of Live Borne Neonate [ Time Frame: Approximately 40 weeks of gestational age. ] [ Designated as safety issue: No ]
    Birth weight of live borne neonates were calculated in grams.

  • Number of Episodes of Symptomatic Malaria Per Participant From First Intermittent Preventive Treatment of Falciparum Dose to Delivery [ Time Frame: Approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
    This outcome measure determined if an episode of malaria started within the time period of first dose to delivery. Clinical episode of malaria was determined if the participant presented with clinical symptoms of malaria (fever >37.5°C, oral) and diagnosed (either by rapid diagnostic tests or microscopy) with malaria.

  • Percentage of Participants Requiring Additional Treatment for Symptomatic Malaria From First Dose to Delivery [ Time Frame: Approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
    This outcome measure evaluated the participants requiring additional treatments for malaria during the study period following the first dose (diagnosed based on clinical presentation and/or lab test results).

  • Percentage of Participants With Peripheral Parasitemia at 36-38 Weeks of Gestation [ Time Frame: At 36-38 weeks of gestation ] [ Designated as safety issue: No ]
    This outcome measure evaluated the percentage of participants positive for peripheral parasitemia at 36-38 weeks of gestation. A participant was positive for parasitemia if the number of asexual parasites per μL was >0.

  • Percentage of Participants With Peripheral Parasitemia at Delivery [ Time Frame: Approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
    This outcome measure evaluated the percentage of participants positive for peripheral parasitemia at delivery. A participant was positive for parasitemia if the number of asexual parasites per μL was >0.

  • Percentage of Participants With Cord Blood Parasitemia at Delivery [ Time Frame: Approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
    This outcome measure evaluated the percentage of participants positive for cord blood parasitemia at delivery. A participant was positive for parasitemia if the number of asexual parasites per μL was >0.

  • Percentage of Participants With Sexually Transmitted Infections From First Dose to 36-38 Weeks of Gestation [ Time Frame: Upto 36-38 weeks of gestation ] [ Designated as safety issue: No ]
    Sexual transmitted disease included Treponema pallidum, Neisseria gonorrhoeae, and Chlamydia trachomatis infections. This was diagnosed based on clinical presentation prior to Week 36-38 and/or lab test results between Week 36-38.

  • Percentage of Participants With Chlamydia Trachomatis Infection at 36-38 Weeks of Gestation [ Time Frame: At 36-38 weeks of gestation ] [ Designated as safety issue: No ]
    Participants positive for Chlamydia trachomatis infection was diagnosed based on laboratory result at 36-38 weeks of gestation. A vaginal swab was collected and PCR assay was used for analysis.

  • Percentage of Participants With Neisseria Gonorrhoeae Infection at 36-38 Weeks of Gestation [ Time Frame: At 36-38 weeks of gestation ] [ Designated as safety issue: No ]
    Participants positive for Neisseria gonorrhoeae infection was diagnosed based on laboratory result at 36-38 weeks of gestation. A vaginal swab was collected and PCR assay was used for analysis.

  • Percentage of Participants With Treponema Pallidum Infection at 36-38 Weeks of Gestation [ Time Frame: At 36-38 weeks of gestation ] [ Designated as safety issue: No ]
    Participants positive for Treponema pallidum infection was diagnosed based on laboratory result at 36-38 weeks of gestation. Treponema Pallidum particle Agglutination Assay was used.

  • Percentage of Participants With Trichomonas Vaginalis Infection at 36-38 Weeks of Gestation [ Time Frame: At 36-38 weeks of gestation ] [ Designated as safety issue: No ]
    Participants positive for Trichomonas vaginalis infection was diagnosed based on laboratory result at 36-38 weeks of gestation. A vaginal swab was collected for the laboratory test.

  • Percentage of Participants With Bacterial Vaginosis Infection at 36-38 Weeks of Gestation. [ Time Frame: At 36-38 weeks of gestation ] [ Designated as safety issue: No ]
    Bacterial vaginosis was diagnosed based on laboratory result at 36-38 weeks of gestation. A vaginal swab was collected for the Gram staining.

  • Percentage of Neonates With Ophthalmia Neonatorum at Birth Period [ Time Frame: Approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
    Ophthalmia neonatorum was diagnosed at birth. The laboratory diagnosis was performed among neonates with purulent discharge.

  • Percentage of Participants With Bacterial Infections Including Pneumonia and Other Lower Respiratory Tract Infections From First Dose to Delivery [ Time Frame: Up to approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
    Participants positive for bacterial infections including other lower respiratory tract infections were measured anytime from first dose administration to delivery.

  • Percentage of Participants With Pre-eclampsia From Week 20 to Delivery [ Time Frame: From Week 20 to approximately 40 weeks of gestational age ] [ Designated as safety issue: No ]
    Pre-eclampsia was diagnosed as systolic blood pressure of at least 140 mmHg and/or diastolic blood pressure of at least 90 mmHg on two separate readings taken at least 4 hours apart and proteinuria at least 300 mg protein in a 24 hour urine collection.

  • Nasopharyngeal Swabs Positive for Macrolide Resistant Streptococcus Pneumoniae [ Time Frame: Visits 6 and 7 ] [ Designated as safety issue: No ]
    This outcome measure evaluated the Streptococcus pneumoniae sensitivity against macrolide antibiotics.

  • Nasopharyngeal Swabs Positive for Penicillin Resistant Streptococcus Pneumoniae [ Time Frame: Visits 6 and 7 ] [ Designated as safety issue: No ]
    This outcome measure evaluated the Streptococcus pneumoniae sensitivity against penicillin antibiotics.


Enrollment: 2891
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
Comité National d'Éthique pour la Recherche en Santé
Cotonou, Benin
Centre de Santé d'AHOUANSORI-AGUE
Cotonou, Benin
Hôpital Bethesda
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
Nyamagana District Hospital
Mwanza, Tanzania
Bugando Medical Centre
Mwanza, Tanzania, 1903
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
Results First Received: August 25, 2014
Last Updated: September 10, 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
Parasitic Diseases
Protozoan Infections
Chloroquine
Chloroquine diphosphate
Fanasil, pyrimethamine drug combination
Pyrimethamine
Sulfadoxine
Amebicides
Analgesics
Analgesics, Non-Narcotic
Anthelmintics
Anti-Infective Agents
Anti-Infective Agents, Urinary
Anti-Inflammatory Agents
Anti-Inflammatory Agents, Non-Steroidal
Antimalarials
Antinematodal Agents
Antiparasitic Agents
Antiprotozoal Agents
Antirheumatic Agents
Central Nervous System Agents
Enzyme Inhibitors
Filaricides
Folic Acid Antagonists
Molecular Mechanisms of Pharmacological Action
Peripheral Nervous System Agents
Pharmacologic Actions
Physiological Effects of Drugs

ClinicalTrials.gov processed this record on October 29, 2014