Intermittent Preventive Treatment With Azithromycin-containing Regimens in Pregnant Women in Papua New Guinea

NCT01136850 | Completed Phase 3 DMC

• 1 other identifier: 70270
• Study Type: interventional
• Target: 2,793
• Locations: 1 country
• Sites: 1

Brief Summary

The purpose of this study is to determine whether repeated courses of sulphadoxine-pyrimethamine (SP) in combination with azithromycin given at Antenatal Clinic, leads to lower rates of low birth weight deliveries (\<2.5 kg) among Papua New Guinean women, than the current standard treatment of SP and chloroquine.

Conditions

Malaria in Pregnancy; Sexually Transmitted Infections; Anaemia

Keywords

Plasmodium falciparum; Plasmodium vivax; azithromycin; sulphadoxine pyrimethamine; low birth weight; haemoglobin; Chlamydia trachomatis; Neisseria gonorrhoeae; Treponema pallidum

Outcome Measures

Primary Outcomes (1)

• Proportion of women delivering low birth weight babies, <2500 g

  At delivery

Secondary Outcomes (11)

• Prevalence of P falciparum at delivery in peripheral, placental and cord blood films and on placental histology

  at delivery

• Mean maternal hemoglobin concentration at delivery, and proportion of women anaemic (Hb < 11 g/dl).

  At delivery

• Prevalence (at enrolment, second treatment, and delivery) and consequences (maternal haemoglobin, birth weight and placental pathology) of P. vivax infection in pregnancy

  up to 26 weeks

• Incidence of symptomatic malaria during pregnancy

  Up to 26 weeks

• Proportion of women carrying azithromycin-sensitive sexually transmitted infections at second treatment visit (28-34 weeks).

  28-34 week gestation study visit

Study Arms (2)

SP, chloroquine treatment; bed net

ACTIVE COMPARATOR

Treatment course of sulphadoxine pyrimethamine and chloroquine on enrolment. Long lasting insecticide treated bed net

Drug: chloroquine, sulphadoxine pyrimethamine, LLIN

3 x SP plus azithromycin; bed nets

EXPERIMENTAL

Three x monthly courses of azithromycin and sulphadoxine pyrimethamine plus long lasting insecticide treated bed net.

Drug: azithromycin, sulphadoxine pyrimethamine, LLIN

Interventions

chloroquine, sulphadoxine pyrimethamine, LLIN DRUG

\> 50Kg: chloroquine base 150 mg 4 tablets daily for 3 days, plus sulphadoxine pyrimethamine 1500/75 mg single dose. \< 50 Kg: chloroquine base 150 mg 3 tablets daily for 3 days, plus sulphadoxine pyrimethamine 1500/75 mg single dose. Given at enrolment, 14-26 weeks gestation, by mouth.

Also known as: sulfadoxine-pyrimethamine

SP, chloroquine treatment; bed net

azithromycin, sulphadoxine pyrimethamine, LLIN DRUG

sulphadoxine pyrimethamine (1500 mg/75 mg as single dose) plus azithromycin (1 g twice daily for 2 days). Given three times by mouth at monthly intervals, commencing at between 14 and 26 weeks gestation.

Also known as: Zithromax, sulfadoxine-pyrimethamine

3 x SP plus azithromycin; bed nets

Eligibility Criteria

• Age: 16 Years - 49 Years
• Sex: female
• Healthy Volunteers: Yes
• Age Groups: Child (0-17), Adult (18-64)

You may qualify if:

• pregnant
• weeks'gestation
• permanent resident of study area
• exclusive use of study health facilities for primary health care
• Age is between 16 and 49 years

You may not qualify if:

• Known chronic illness, e.g. TB, diabetes, renal failure
• Severe anaemia requiring hospitalisation (Hb \< 6 g/dl accompanied by symptoms requiring urgent treatment)
• permanent disability, that prevents or impedes study participation and/or comprehension
• Known multiple pregnancy

Sponsors & Collaborators

• University of Melbourne: lead
• Papua New Guinea Institute of Medical Research: collaborator
• The University of Western Australia: collaborator
• Walter and Eliza Hall Institute of Medical Research: collaborator
• University of Barcelona: collaborator

Study Sites (1)

Papua New Guinea Institute of Medical Research

Madang, Madang Province, Papua New Guinea

Location

Related Publications (19)

• Steketee RW, Nahlen BL, Parise ME, Menendez C. The burden of malaria in pregnancy in malaria-endemic areas. Am J Trop Med Hyg. 2001 Jan-Feb;64(1-2 Suppl):28-35. doi: 10.4269/ajtmh.2001.64.28.

  PMID: 11425175 BACKGROUND

• Guyatt HL, Snow RW. The epidemiology and burden of Plasmodium falciparum-related anemia among pregnant women in sub-Saharan Africa. Am J Trop Med Hyg. 2001 Jan-Feb;64(1-2 Suppl):36-44. doi: 10.4269/ajtmh.2001.64.36.

  PMID: 11425176 BACKGROUND

• Brabin B, Piper C. Anaemia- and malaria-attributable low birthweight in two populations in Papua New Guinea. Ann Hum Biol. 1997 Nov-Dec;24(6):547-55. doi: 10.1080/03014469700005312.

  PMID: 9395740 BACKGROUND

• Benet A, Khong TY, Ura A, Samen R, Lorry K, Mellombo M, Tavul L, Baea K, Rogerson SJ, Cortes A. Placental malaria in women with South-East Asian ovalocytosis. Am J Trop Med Hyg. 2006 Oct;75(4):597-604.

  PMID: 17038679 BACKGROUND

• Allen SJ, Raiko A, O'Donnell A, Alexander ND, Clegg JB. Causes of preterm delivery and intrauterine growth retardation in a malaria endemic region of Papua New Guinea. Arch Dis Child Fetal Neonatal Ed. 1998 Sep;79(2):F135-40. doi: 10.1136/fn.79.2.f135.

  PMID: 9828741 BACKGROUND

• Schultz LJ, Steketee RW, Macheso A, Kazembe P, Chitsulo L, Wirima JJ. The efficacy of antimalarial regimens containing sulfadoxine-pyrimethamine and/or chloroquine in preventing peripheral and placental Plasmodium falciparum infection among pregnant women in Malawi. Am J Trop Med Hyg. 1994 Nov;51(5):515-22. doi: 10.4269/ajtmh.1994.51.515.

  PMID: 7985742 BACKGROUND

• Parise ME, Ayisi JG, Nahlen BL, Schultz LJ, Roberts JM, Misore A, Muga R, Oloo AJ, Steketee RW. Efficacy of sulfadoxine-pyrimethamine for prevention of placental malaria in an area of Kenya with a high prevalence of malaria and human immunodeficiency virus infection. Am J Trop Med Hyg. 1998 Nov;59(5):813-22. doi: 10.4269/ajtmh.1998.59.813.

  PMID: 9840604 BACKGROUND

• Verhoeff FH, Brabin BJ, Chimsuku L, Kazembe P, Russell WB, Broadhead RL. An evaluation of the effects of intermittent sulfadoxine-pyrimethamine treatment in pregnancy on parasite clearance and risk of low birthweight in rural Malawi. Ann Trop Med Parasitol. 1998 Mar;92(2):141-50. doi: 10.1080/00034989859979.

  PMID: 9625909 BACKGROUND

• Shulman CE, Dorman EK, Cutts F, Kawuondo K, Bulmer JN, Peshu N, Marsh K. Intermittent sulphadoxine-pyrimethamine to prevent severe anaemia secondary to malaria in pregnancy: a randomised placebo-controlled trial. Lancet. 1999 Feb 20;353(9153):632-6. doi: 10.1016/s0140-6736(98)07318-8.

  PMID: 10030329 BACKGROUND

• Casey GJ, Ginny M, Uranoli M, Mueller I, Reeder JC, Genton B, Cowman AF. Molecular analysis of Plasmodium falciparum from drug treatment failure patients in Papua New Guinea. Am J Trop Med Hyg. 2004 Mar;70(3):251-5.

  PMID: 15031512 BACKGROUND

• ter Kuile FO, van Eijk AM, Filler SJ. Effect of sulfadoxine-pyrimethamine resistance on the efficacy of intermittent preventive therapy for malaria control during pregnancy: a systematic review. JAMA. 2007 Jun 20;297(23):2603-16. doi: 10.1001/jama.297.23.2603.

  PMID: 17579229 BACKGROUND

• Kalilani L, Mofolo I, Chaponda M, Rogerson SJ, Alker AP, Kwiek JJ, Meshnick SR. A randomized controlled pilot trial of azithromycin or artesunate added to sulfadoxine-pyrimethamine as treatment for malaria in pregnant women. PLoS One. 2007 Nov 14;2(11):e1166. doi: 10.1371/journal.pone.0001166.

  PMID: 18000538 BACKGROUND

• Unger HW, Bleicher A, Ome-Kaius M, Aitken EH, Rogerson SJ. Associations of maternal iron deficiency with malaria infection in a cohort of pregnant Papua New Guinean women. Malar J. 2022 May 26;21(1):153. doi: 10.1186/s12936-022-04177-8.

  PMID: 35619134 DERIVED

• Unger HW, Laurita Longo V, Bleicher A, Ome-Kaius M, Karl S, Simpson JA, Karahalios A, Aitken EH, Rogerson SJ. The relationship between markers of antenatal iron stores and birth outcomes differs by malaria prevention regimen-a prospective cohort study. BMC Med. 2021 Oct 5;19(1):236. doi: 10.1186/s12916-021-02114-1.

  PMID: 34607575 DERIVED

• Aitken EH, Damelang T, Ortega-Pajares A, Alemu A, Hasang W, Dini S, Unger HW, Ome-Kaius M, Nielsen MA, Salanti A, Smith J, Kent S, Hogarth PM, Wines BD, Simpson JA, Chung AW, Rogerson SJ. Developing a multivariate prediction model of antibody features associated with protection of malaria-infected pregnant women from placental malaria. Elife. 2021 Jun 29;10:e65776. doi: 10.7554/eLife.65776.

  PMID: 34181872 DERIVED

• Ome-Kaius M, Karl S, Wangnapi RA, Bolnga JW, Mola G, Walker J, Mueller I, Unger HW, Rogerson SJ. Effects of Plasmodium falciparum infection on umbilical artery resistance and intrafetal blood flow distribution: a Doppler ultrasound study from Papua New Guinea. Malar J. 2017 Jan 19;16(1):35. doi: 10.1186/s12936-017-1689-z.

  PMID: 28103875 DERIVED

• Ome-Kaius M, Unger HW, Singirok D, Wangnapi RA, Hanieh S, Umbers AJ, Elizah J, Siba P, Mueller I, Rogerson SJ. Determining effects of areca (betel) nut chewing in a prospective cohort of pregnant women in Madang Province, Papua New Guinea. BMC Pregnancy Childbirth. 2015 Aug 19;15:177. doi: 10.1186/s12884-015-0615-z.

  PMID: 26286026 DERIVED

• Teo A, Hasang W, Randall LM, Unger HW, Siba PM, Mueller I, Brown GV, Rogerson SJ. Malaria preventive therapy in pregnancy and its potential impact on immunity to malaria in an area of declining transmission. Malar J. 2015 May 26;14:215. doi: 10.1186/s12936-015-0736-x.

  PMID: 26006260 DERIVED

• Unger HW, Ome-Kaius M, Wangnapi RA, Umbers AJ, Hanieh S, Suen CS, Robinson LJ, Rosanas-Urgell A, Wapling J, Lufele E, Kongs C, Samol P, Sui D, Singirok D, Bardaji A, Schofield L, Menendez C, Betuela I, Siba P, Mueller I, Rogerson SJ. Sulphadoxine-pyrimethamine plus azithromycin for the prevention of low birthweight in Papua New Guinea: a randomised controlled trial. BMC Med. 2015 Jan 16;13:9. doi: 10.1186/s12916-014-0258-3.

  PMID: 25591391 DERIVED

Related Links

• home page of umbrella organisation coordinating this and other trials on malaria in pregnancy
• home page of Department of Central contact person, Dr Rogerson
• home page of Papua New Guinea Institute of Medical Research

MeSH Terms

Conditions

Sexually Transmitted Diseases; Anemia; Malaria, Falciparum; Malaria, Vivax; Treponemal Infections

Interventions

Chloroquine; fanasil, pyrimethamine drug combination; Azithromycin

Condition Hierarchy (Ancestors)

Communicable Diseases; Infections; Genital Diseases; Urogenital Diseases; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Hematologic Diseases; Hemic and Lymphatic Diseases; Malaria; Protozoan Infections; Parasitic Diseases; Mosquito-Borne Diseases; Vector Borne Diseases; Spirochaetales Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses

Intervention Hierarchy (Ancestors)

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

Study Officials

• Stephen J Rogerson, FRACP PhD

  University of Melbourne

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Medicine

Study Record Dates

• First Submitted: April 6, 2010
• First Posted: June 4, 2010
• Study Start: November 1, 2009
• Primary Completion: December 1, 2012
• Study Completion: January 1, 2013
• Last Updated: April 23, 2013

Record last verified: 2013-04

Locations

PA (1)