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

Purpose

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	Intervention	Phase
Malaria in Pregnancy Sexually Transmitted Infections Anaemia	Drug: chloroquine, sulphadoxine pyrimethamine, LLIN Drug: azithromycin, sulphadoxine pyrimethamine, LLIN	Phase 3

Study Type:	Interventional
Study Design:	Allocation: Randomized Endpoint Classification: Efficacy Study Intervention Model: Parallel Assignment Masking: Single Blind (Subject) 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

Resource links provided by NLM:

MedlinePlus related topics: Anemia Birth Weight Malaria Sexually Transmitted Diseases

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

U.S. FDA Resources

Further study details as provided by University of Melbourne:

Primary Outcome Measures:

Proportion of women delivering low birth weight babies, <2500 g [ Time Frame: At delivery ] [ Designated as safety issue: No ]

Secondary Outcome Measures:

Prevalence of P falciparum at delivery in peripheral, placental and cord blood films and on placental histology [ Time Frame: at delivery ] [ Designated as safety issue: No ]
Mean maternal hemoglobin concentration at delivery, and proportion of women anaemic (Hb < 11 g/dl). [ Time Frame: At delivery ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
From enrolment at 14-26 weeks gestation, until delivery
Incidence of symptomatic malaria during pregnancy [ Time Frame: Up to 26 weeks ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Incidence of Adverse Events, including severe adverse events (SAEs), and AEs possibly or probably associated with study medications [ Time Frame: 14-26 weeks ] [ Designated as safety issue: Yes ]
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 ] [ Designated as safety issue: No ]
Prevalence and antibiotic sensitivity patterns of S. pneumoniae in nasopharyngeal swabs collected at delivery [ Time Frame: at delivery ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
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 ] [ Designated as safety issue: No ]
Characteristics of parasites infecting pregnant women [ Time Frame: Up to 26 weeks, from 14-26 weeks gestation until delivery ] [ Designated as safety issue: No ]

Enrollment:	2793
Study Start Date:	November 2009
Study Completion Date:	January 2013
Primary Completion Date:	December 2012 (Final data collection date for primary outcome measure)

Arms	Assigned Interventions
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

Eligibility

Ages Eligible for Study:	16 Years to 49 Years
Genders 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

Please refer to this study by its ClinicalTrials.gov identifier: NCT01136850

Locations

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

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. Review.

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. Review.

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.

Benet A, Khong TY, Ura A, Samen R, Lorry K, Mellombo M, Tavul L, Baea K, Rogerson SJ, Cortés 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.

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.

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.

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.

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.

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. Review.

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.

Responsible Party:	Stephen Rogerson, Professor of Medicine, University of Melbourne
ClinicalTrials.gov Identifier:	NCT01136850 History of Changes
Other Study ID Numbers:	70270
Study First Received:	April 6, 2010
Last Updated:	April 20, 2013
Health Authority:	Papua New Guinea: Papua New Guinea Medical Research Advisory Council

Keywords provided by University of Melbourne:

Plasmodium falciparum
Plasmodium vivax
azithromycin
sulphadoxine pyrimethamine
low birth weight

haemoglobin
Chlamydia trachomatis
Neisseria gonorrhoeae
Treponema pallidum

Additional relevant MeSH terms:

Anemia
Malaria
Sexually Transmitted Diseases
Hematologic Diseases
Protozoan Infections
Parasitic Diseases
Infection
Virus Diseases
Genital Diseases, Male
Genital Diseases, Female
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

ClinicalTrials.gov processed this record on May 22, 2013

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