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

NCT01103063 | Terminated Phase 3 Results DMC

• 1 other identifier: A0661158
• Study Type: interventional
• Target: 2,891
• Locations: 5 countries
• Sites: 9

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.

Conditions

Intermittent Preventive Treatment In Pregnancy (IPTp)

Keywords

P. falciparum malaria; IPTp

Outcome Measures

Primary Outcomes (1)

• Percentage Participants With Sub-optimal Pregnancy Outcome in Intent-to-Treat (IIT) Population

  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.

  Approximately 40 weeks of gestational age

Secondary Outcomes (29)

• Percentage of Participants With Sub-optimal Pregnancy Outcome in Efficacy Analyzable Per Protocol (PP) Population

  Approximately 40 weeks of gestational age

• Percentage of Neonates With LBW (<2500 g) in ITT Population

  Approximately 40 weeks of gestational age

• Percentage of Neonates With LBW (<2500 g) in Efficacy Analyzable PP Population

  Approximately 40 weeks of gestational age

• Percentage of Participants With Severe Maternal Anemia (Hemoglobin [Hb] <8 g/dL) at 36-38 Weeks of Gestation

  At 36-38 weeks of gestation.

• Percentage of Participants With Maternal Anemia (Hb <11 g/dL) at 36-38 Weeks of Gestation

  At 36-38 weeks of gestation.

Study Arms (2)

AZCQ

EXPERIMENTAL

Azithromycin/chloroquine

Drug: Azithromycin plus chloroquine

SP

ACTIVE COMPARATOR

sulfadoxine-pyrimethamine (Fansidar)

Drug: sulfadoxine-pyrimethamine

Interventions

Azithromycin plus chloroquine DRUG

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.

AZCQ

sulfadoxine-pyrimethamine DRUG

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.

Also known as: Fansidar

SP

Eligibility Criteria

• Age: 16 Years - 35 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• 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.

You may not qualify if:

• 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.

Sponsors & Collaborators

• Pfizer: lead
• London School of Hygiene and Tropical Medicine: collaborator
• Medicines for Malaria Venture: collaborator

Study Sites (9)

Centre de Santé d'AHOUANSORI-AGUE

Cotonou, Benin, Benin

Location

Hôpital Bethesda

Cotonou, Benin

Location

Siaya District Hospital

Siaya, Siaya County, Kenya

Location

Zomba Central Hospital

Zomba, Malawi

Location

Teule Hospital

Muheza, Tanga, Tanzania

Location

Nyamagana District Hospital

Mwanza, Tanzania, Tanzania

Location

Bugando Medical Centre

Mwanza, 1903, Tanzania

Location

Nyamagana District Hospital, c/o National Institute for Medical Research, Mwanza Centre

Mwanza, Tanzania

Location

Mulago Hospital Complex

Kampala, Uganda

Location

Related Publications (2)

• 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.

  PMID: 29566732 DERIVED

• 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.

  PMID: 27326859 DERIVED

Related Links

• To obtain contact information for a study center near you, click here.

MeSH Terms

Interventions

Azithromycin; Chloroquine; fanasil, pyrimethamine drug combination

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals; Aminoquinolines; Quinolines; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds

Limitations and Caveats

This program was terminated by Pfizer based on the results of the pre-planned interim analysis for this pivotal study. The interim analysis showed no benefit of the study drug (AZCQ) compared to standard of care (SP).

Results Point of Contact

• Title: Pfizer ClinicalTrials.gov Call Center
• Organization: Pfizer, Inc.

ClinicalTrials.gov_Inquiries@pfizer.com

1-800-718-1021

Study Officials

• Pfizer CT.gov Call Center

  Pfizer

  STUDY DIRECTOR

Publication Agreements

• PI is Sponsor Employee: No
• Restriction Type: OTHER
• Restrictive Agreement: Yes

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: INDUSTRY
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 7, 2010
• First Posted: April 13, 2010
• Study Start: October 1, 2010
• Primary Completion: October 1, 2013
• Study Completion: November 1, 2013
• Last Updated: June 16, 2015
• Results First Posted: September 5, 2014

Record last verified: 2015-05

Locations

TA (4); MA (1); KE (1); UG (1); BE (2)