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

Anaemia Clinical Trial

— IPTp in PNG  

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT01136850
• Other study ID #: 70270
• Status: Completed
• Phase: Phase 3
• First received: April 6, 2010
• Last updated: April 20, 2013
• Start date: November 2009
• Est. completion date: January 2013

Study information

• Verified date: April 2013
• Source: University of Melbourne
• Contact: n/a
• Is FDA regulated: No
• Health authority: Papua New Guinea: Papua New Guinea Medical Research Advisory Council
• Study type: Interventional

Clinical Trial 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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 2793
• Est. completion date: January 2013
• Est. primary completion date: December 2012
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Female
• Age group: 16 Years to 49 Years

Eligibility

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

Study Design

Allocation: Randomized, Endpoint Classification: Efficacy Study, Intervention Model: Parallel Assignment, Masking: Single Blind (Subject), Primary Purpose: Prevention

Related Conditions & MeSH terms

• Anaemia
• Malaria
• Malaria in Pregnancy
• Sexually Transmitted Diseases
• Sexually Transmitted Infections

Intervention

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.
• 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.

Locations

Country	Name	City	State
Papua New Guinea	Papua New Guinea Institute of Medical Research	Madang	Madang Province

Sponsors (5)

Lead Sponsor	Collaborator
University of Melbourne	Papua New Guinea Institute of Medical Research, The University of Western Australia, University of Barcelona, Walter and Eliza Hall Institute of Medical Research

Country where clinical trial is conducted

Papua New Guinea, 

References & Publications (12)

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

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. — View Citation

* Note: There are 12 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Proportion of women delivering low birth weight babies, <2500 g		At delivery	No
Secondary	Prevalence of P falciparum at delivery in peripheral, placental and cord blood films and on placental histology		at delivery	No
Secondary	Mean maternal hemoglobin concentration at delivery, and proportion of women anaemic (Hb < 11 g/dl).		At delivery	No
Secondary	Prevalence (at enrolment, second treatment, and delivery) and consequences (maternal haemoglobin, birth weight and placental pathology) of P. vivax infection in pregnancy	From enrolment at 14-26 weeks gestation, until delivery	up to 26 weeks	No
Secondary	Incidence of symptomatic malaria during pregnancy	From enrolment at 14-26 weeks until delivery	Up to 26 weeks	No
Secondary	Proportion of women carrying azithromycin-sensitive sexually transmitted infections at second treatment visit (28-34 weeks).		28-34 week gestation study visit	No
Secondary	Incidence of Adverse Events, including severe adverse events (SAEs), and AEs possibly or probably associated with study medications	From enrolment at 14-26 weeks gestation until delivery	14-26 weeks	Yes
Secondary	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		at delivery	No
Secondary	Prevalence and antibiotic sensitivity patterns of S. pneumoniae in nasopharyngeal swabs collected at delivery		at delivery	No
Secondary	Maternal, perinatal and infant mortality rates	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	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	No
Secondary	Impact of IPTp on development of immunity to malaria in pregnancy		at delivery	No
Secondary	Characteristics of parasites infecting pregnant women		Up to 26 weeks, from 14-26 weeks gestation until delivery	No

External Links

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