Intermittent Preventive Treatment With Azithromycin-containing Regimens in Pregnant Women in Papua New Guinea (IPTp in PNG)

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ClinicalTrials.gov Identifier: NCT01136850

Recruitment Status : Completed

First Posted : June 4, 2010

Last Update Posted : April 23, 2013

View this study on Beta.ClinicalTrials.gov

Sponsor:

Collaborators:

Papua New Guinea Institute of Medical Research

The University of Western Australia

Walter and Eliza Hall Institute of Medical Research

University of Barcelona

Information provided by (Responsible Party):

Stephen Rogerson, University of Melbourne

Study Description

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.

Condition or disease	Intervention/treatment	Phase
Malaria in Pregnancy Sexually Transmitted Infections Anaemia	Drug: chloroquine, sulphadoxine pyrimethamine, LLIN Drug: azithromycin, sulphadoxine pyrimethamine, LLIN	Phase 3

Study Design

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Study Type :	Interventional (Clinical Trial)
Actual Enrollment :	2793 participants
Allocation:	Randomized
Intervention Model:	Parallel Assignment
Masking:	Single (Participant)
Primary Purpose:	Prevention
Official Title:	Intermittent Preventive Treatment With Azithromycin-containing Regimens for the Prevention of Malarial Infections and Anaemia and the Control of Sexually Transmitted Infections in Pregnant Women in Papua New Guinea
Study Start Date :	November 2009
Actual Primary Completion Date :	December 2012
Actual Study Completion Date :	January 2013

Resource links provided by the National Library of Medicine

MedlinePlus related topics: Pregnancy

Drug Information available for: Chloroquine phosphate Chloroquine Pyrimethamine Chloroquine sulfate Chloroquine hydrochloride Azithromycin Azithromycin dihydrate Azithromycin monohydrate

Genetic and Rare Diseases Information Center resources: Malaria Treponema Infection

U.S. FDA Resources

Arms and Interventions

Arm	Intervention/treatment
Active Comparator: SP, chloroquine treatment; bed net Treatment course of sulphadoxine pyrimethamine and chloroquine on enrolment. Long lasting insecticide treated bed net	Drug: chloroquine, sulphadoxine pyrimethamine, LLIN > 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. Other Name: sulfadoxine-pyrimethamine
Experimental: 3 x SP plus azithromycin; bed nets Three x monthly courses of azithromycin and sulphadoxine pyrimethamine plus long lasting insecticide treated bed net.	Drug: azithromycin, sulphadoxine pyrimethamine, LLIN 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. Other Names: Zithromax sulfadoxine-pyrimethamine

Outcome Measures

Primary Outcome Measures :

Proportion of women delivering low birth weight babies, <2500 g [ Time Frame: At delivery ]

Secondary Outcome Measures :

Prevalence of P falciparum at delivery in peripheral, placental and cord blood films and on placental histology [ Time Frame: at delivery ]
Mean maternal hemoglobin concentration at delivery, and proportion of women anaemic (Hb < 11 g/dl). [ Time Frame: At delivery ]
Prevalence (at enrolment, second treatment, and delivery) and consequences (maternal haemoglobin, birth weight and placental pathology) of P. vivax infection in pregnancy [ Time Frame: up to 26 weeks ]
From enrolment at 14-26 weeks gestation, until delivery
Incidence of symptomatic malaria during pregnancy [ Time Frame: Up to 26 weeks ]
From enrolment at 14-26 weeks until delivery
Proportion of women carrying azithromycin-sensitive sexually transmitted infections at second treatment visit (28-34 weeks). [ Time Frame: 28-34 week gestation study visit ]
Incidence of Adverse Events, including severe adverse events (SAEs), and AEs possibly or probably associated with study medications [ Time Frame: 14-26 weeks ]
From enrolment at 14-26 weeks gestation until delivery
Prevalence of drug resistance markers in parasites infecting women in late pregnancy, particularly in the P falciparum and P vivax dihydrofolate reductase and dihydropteroate synthase enzymes, associated with SP resistance [ Time Frame: at delivery ]
Prevalence and antibiotic sensitivity patterns of S. pneumoniae in nasopharyngeal swabs collected at delivery [ Time Frame: at delivery ]
Maternal, perinatal and infant mortality rates [ Time Frame: Mothers; up to 32 weeks, from enrolment at 14-26 weeks gestation, until delivery. Pernatal: 16 weeks, from 28 weeks gestation to 4 weeks of age. Infant: from live birth to 1 year of age ]
maternal mortality is during pregnancy and until 6 weeks post partum. Perinatal mortality is from 28 weeks gestation until 6 weeks postpartum. Infant mortality is from irth to 12 months of age
Impact of IPTp on development of immunity to malaria in pregnancy [ Time Frame: at delivery ]
Characteristics of parasites infecting pregnant women [ Time Frame: Up to 26 weeks, from 14-26 weeks gestation until delivery ]

Eligibility Criteria

Information from the National Library of Medicine

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Ages Eligible for Study:	16 Years to 49 Years (Child, Adult)
Sexes Eligible for Study:	Female
Accepts Healthy Volunteers:	Yes

Criteria

Inclusion Criteria:

pregnant
14-26 weeks'gestation
permanent resident of study area
exclusive use of study health facilities for primary health care
Age is between 16 and 49 years

Exclusion Criteria:

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

Contacts and Locations

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01136850

Locations

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Papua New Guinea
Papua New Guinea Institute of Medical Research
Madang, Madang Province, Papua New Guinea

Sponsors and Collaborators

University of Melbourne

Papua New Guinea Institute of Medical Research

The University of Western Australia

Walter and Eliza Hall Institute of Medical Research

University of Barcelona

Investigators

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Principal Investigator:	Stephen J Rogerson, FRACP PhD	University of Melbourne

More Information

Additional Information:

home page of umbrella organisation coordinating this and other trials on malaria in pregnancy This link exits the ClinicalTrials.gov site

home page of Department of Central contact person, Dr Rogerson This link exits the ClinicalTrials.gov site

home page of Papua New Guinea Institute of Medical Research This link exits the ClinicalTrials.gov site

Publications:

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

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.

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.

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.

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.

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.

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.

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.

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Responsible Party:	Stephen Rogerson, Professor of Medicine, University of Melbourne
ClinicalTrials.gov Identifier:	NCT01136850
Other Study ID Numbers:	70270
First Posted:	June 4, 2010 Key Record Dates
Last Update Posted:	April 23, 2013
Last Verified:	April 2013

Keywords provided by Stephen Rogerson, University of Melbourne:


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

Additional relevant MeSH terms:

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Infections Sexually Transmitted Diseases Anemia Communicable Diseases Disease Attributes Pathologic Processes Hematologic Diseases Azithromycin Chloroquine Pyrimethamine Sulfadoxine Fanasil, pyrimethamine drug combination	Anti-Bacterial Agents Anti-Infective Agents Amebicides Antiprotozoal Agents Antiparasitic Agents Antimalarials Antirheumatic Agents Folic Acid Antagonists Enzyme Inhibitors Molecular Mechanisms of Pharmacological Action Anti-Infective Agents, Urinary Renal Agents

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