A randomized open-label evaluation of the antimalarial prophylactic efficacy of azithromycin-piperaquine versus sulfadoxine-pyrimethamine in pregnant papua new guinean women

Brioni R. Moore, John M. Benjamin, Roselyn Tobe, Maria Ome-Kaius, Gumul Yadi, Bernadine Kasian, Charles Kong, Leanne J. Robinson, Moses Laman, Ivo Mueller, Stephen Rogerson, Timothy M.E. Davis

Research output: Contribution to journalArticle

Abstract

Emerging malaria parasite sulfadoxine-pyrimethamine (SP) resistance has prompted assessment of alternatives for intermittent preventive treatment in pregnancy (IPTp). The objective was to evaluate the tolerability and prophylactic efficacy of azithromycin (AZ) plus piperaquine (PQ) in pregnant women in Papua New Guinea. The study was an open-label, randomized, parallel-group trial. A total of 122 women (median gestation, 26 weeks [range, 14 to 32 weeks]) were randomized 1:1 to three daily doses of 1 g AZ plus 960 mg PQ tetraphosphate or single-dose SP (4,500 mg sulfadoxine plus 225 mg pyrimethamine), based on computer-generated block randomization. Tolerability was assessed to day 7, and efficacy was assessed to day 42 (when participants were returned to usual care) and at delivery. Data for 119 participants (AZ-PQ, n = 61; SP, n = 58) were analyzed. Both regimens were well tolerated, but AZ-PQ was associated with more gastrointestinal side effects (31%) and dizziness (21%). Eight women (6.7%) were parasitemic at recruitment but all were aparasitemic by 72 h. There were no differences in blood smear positivity rates between AZ-PQ and SP up to day 42 (0% versus 5.2%; relative risk [RR], 0.14 [95% confidence interval [CI], 0.01 to 2.58] [P = 0.18]; absolute risk reduction [ARR], 5.2% [95% CI, -1.3 to 11.6%]) and at the time of delivery (0% versus 8.7%; RR, 0.11 [95% CI, 0.01 to 2.01] [P = 0.14]; ARR, 8.7% [95% CI, -0.2 to 17.6%]). Of 92 women who were monitored to parturition, 89 (97%) delivered healthy babies; there were 3 stillbirths (SP, n = 1; AZ-PQ, n = 2 [twins]). There was a higher live birth weight (mean ± standard deviation) in the AZ-PQ group (3.13 ± 0.42 versus 2.88 ± 0.55 kg [P = 0.016]; mean difference, 0.25 kg [95% CI, 0.02 to 0.48 kg]). AZ-PQ is a promising candidate for IPTp.

Original languageEnglish
Article numbere00302-19
JournalAntimicrobial Agents and Chemotherapy
Volume63
Issue number10
DOIs
Publication statusPublished - 1 Jan 2019

Fingerprint

Azithromycin
Antimalarials
Confidence Intervals
Numbers Needed To Treat
Pregnancy
Sulfadoxine
Papua New Guinea
Pyrimethamine
Stillbirth
pyrimethamine drug combination fanasil
piperaquine
Live Birth
Dizziness
Random Allocation
Birth Weight
Malaria
Pregnant Women
Parasites
Parturition
Therapeutics

Cite this

Moore, Brioni R. ; Benjamin, John M. ; Tobe, Roselyn ; Ome-Kaius, Maria ; Yadi, Gumul ; Kasian, Bernadine ; Kong, Charles ; Robinson, Leanne J. ; Laman, Moses ; Mueller, Ivo ; Rogerson, Stephen ; Davis, Timothy M.E. / A randomized open-label evaluation of the antimalarial prophylactic efficacy of azithromycin-piperaquine versus sulfadoxine-pyrimethamine in pregnant papua new guinean women. In: Antimicrobial Agents and Chemotherapy. 2019 ; Vol. 63, No. 10.
@article{37bb94ceccaa4f0ca4c8cecbe6de4f37,
title = "A randomized open-label evaluation of the antimalarial prophylactic efficacy of azithromycin-piperaquine versus sulfadoxine-pyrimethamine in pregnant papua new guinean women",
abstract = "Emerging malaria parasite sulfadoxine-pyrimethamine (SP) resistance has prompted assessment of alternatives for intermittent preventive treatment in pregnancy (IPTp). The objective was to evaluate the tolerability and prophylactic efficacy of azithromycin (AZ) plus piperaquine (PQ) in pregnant women in Papua New Guinea. The study was an open-label, randomized, parallel-group trial. A total of 122 women (median gestation, 26 weeks [range, 14 to 32 weeks]) were randomized 1:1 to three daily doses of 1 g AZ plus 960 mg PQ tetraphosphate or single-dose SP (4,500 mg sulfadoxine plus 225 mg pyrimethamine), based on computer-generated block randomization. Tolerability was assessed to day 7, and efficacy was assessed to day 42 (when participants were returned to usual care) and at delivery. Data for 119 participants (AZ-PQ, n = 61; SP, n = 58) were analyzed. Both regimens were well tolerated, but AZ-PQ was associated with more gastrointestinal side effects (31{\%}) and dizziness (21{\%}). Eight women (6.7{\%}) were parasitemic at recruitment but all were aparasitemic by 72 h. There were no differences in blood smear positivity rates between AZ-PQ and SP up to day 42 (0{\%} versus 5.2{\%}; relative risk [RR], 0.14 [95{\%} confidence interval [CI], 0.01 to 2.58] [P = 0.18]; absolute risk reduction [ARR], 5.2{\%} [95{\%} CI, -1.3 to 11.6{\%}]) and at the time of delivery (0{\%} versus 8.7{\%}; RR, 0.11 [95{\%} CI, 0.01 to 2.01] [P = 0.14]; ARR, 8.7{\%} [95{\%} CI, -0.2 to 17.6{\%}]). Of 92 women who were monitored to parturition, 89 (97{\%}) delivered healthy babies; there were 3 stillbirths (SP, n = 1; AZ-PQ, n = 2 [twins]). There was a higher live birth weight (mean ± standard deviation) in the AZ-PQ group (3.13 ± 0.42 versus 2.88 ± 0.55 kg [P = 0.016]; mean difference, 0.25 kg [95{\%} CI, 0.02 to 0.48 kg]). AZ-PQ is a promising candidate for IPTp.",
keywords = "Azithromycin, Efficacy, Malaria, Piperaquine, Pregnancy, Tolerability",
author = "Moore, {Brioni R.} and Benjamin, {John M.} and Roselyn Tobe and Maria Ome-Kaius and Gumul Yadi and Bernadine Kasian and Charles Kong and Robinson, {Leanne J.} and Moses Laman and Ivo Mueller and Stephen Rogerson and Davis, {Timothy M.E.}",
year = "2019",
month = "1",
day = "1",
doi = "10.1128/AAC.00302-19",
language = "English",
volume = "63",
journal = "Antimicrobial Agents and Chemotherapy",
issn = "0066-4804",
publisher = "American Society for Microbiology",
number = "10",

}

A randomized open-label evaluation of the antimalarial prophylactic efficacy of azithromycin-piperaquine versus sulfadoxine-pyrimethamine in pregnant papua new guinean women. / Moore, Brioni R.; Benjamin, John M.; Tobe, Roselyn; Ome-Kaius, Maria; Yadi, Gumul; Kasian, Bernadine; Kong, Charles; Robinson, Leanne J.; Laman, Moses; Mueller, Ivo; Rogerson, Stephen; Davis, Timothy M.E.

In: Antimicrobial Agents and Chemotherapy, Vol. 63, No. 10, e00302-19, 01.01.2019.

Research output: Contribution to journalArticle

TY - JOUR

T1 - A randomized open-label evaluation of the antimalarial prophylactic efficacy of azithromycin-piperaquine versus sulfadoxine-pyrimethamine in pregnant papua new guinean women

AU - Moore, Brioni R.

AU - Benjamin, John M.

AU - Tobe, Roselyn

AU - Ome-Kaius, Maria

AU - Yadi, Gumul

AU - Kasian, Bernadine

AU - Kong, Charles

AU - Robinson, Leanne J.

AU - Laman, Moses

AU - Mueller, Ivo

AU - Rogerson, Stephen

AU - Davis, Timothy M.E.

PY - 2019/1/1

Y1 - 2019/1/1

N2 - Emerging malaria parasite sulfadoxine-pyrimethamine (SP) resistance has prompted assessment of alternatives for intermittent preventive treatment in pregnancy (IPTp). The objective was to evaluate the tolerability and prophylactic efficacy of azithromycin (AZ) plus piperaquine (PQ) in pregnant women in Papua New Guinea. The study was an open-label, randomized, parallel-group trial. A total of 122 women (median gestation, 26 weeks [range, 14 to 32 weeks]) were randomized 1:1 to three daily doses of 1 g AZ plus 960 mg PQ tetraphosphate or single-dose SP (4,500 mg sulfadoxine plus 225 mg pyrimethamine), based on computer-generated block randomization. Tolerability was assessed to day 7, and efficacy was assessed to day 42 (when participants were returned to usual care) and at delivery. Data for 119 participants (AZ-PQ, n = 61; SP, n = 58) were analyzed. Both regimens were well tolerated, but AZ-PQ was associated with more gastrointestinal side effects (31%) and dizziness (21%). Eight women (6.7%) were parasitemic at recruitment but all were aparasitemic by 72 h. There were no differences in blood smear positivity rates between AZ-PQ and SP up to day 42 (0% versus 5.2%; relative risk [RR], 0.14 [95% confidence interval [CI], 0.01 to 2.58] [P = 0.18]; absolute risk reduction [ARR], 5.2% [95% CI, -1.3 to 11.6%]) and at the time of delivery (0% versus 8.7%; RR, 0.11 [95% CI, 0.01 to 2.01] [P = 0.14]; ARR, 8.7% [95% CI, -0.2 to 17.6%]). Of 92 women who were monitored to parturition, 89 (97%) delivered healthy babies; there were 3 stillbirths (SP, n = 1; AZ-PQ, n = 2 [twins]). There was a higher live birth weight (mean ± standard deviation) in the AZ-PQ group (3.13 ± 0.42 versus 2.88 ± 0.55 kg [P = 0.016]; mean difference, 0.25 kg [95% CI, 0.02 to 0.48 kg]). AZ-PQ is a promising candidate for IPTp.

AB - Emerging malaria parasite sulfadoxine-pyrimethamine (SP) resistance has prompted assessment of alternatives for intermittent preventive treatment in pregnancy (IPTp). The objective was to evaluate the tolerability and prophylactic efficacy of azithromycin (AZ) plus piperaquine (PQ) in pregnant women in Papua New Guinea. The study was an open-label, randomized, parallel-group trial. A total of 122 women (median gestation, 26 weeks [range, 14 to 32 weeks]) were randomized 1:1 to three daily doses of 1 g AZ plus 960 mg PQ tetraphosphate or single-dose SP (4,500 mg sulfadoxine plus 225 mg pyrimethamine), based on computer-generated block randomization. Tolerability was assessed to day 7, and efficacy was assessed to day 42 (when participants were returned to usual care) and at delivery. Data for 119 participants (AZ-PQ, n = 61; SP, n = 58) were analyzed. Both regimens were well tolerated, but AZ-PQ was associated with more gastrointestinal side effects (31%) and dizziness (21%). Eight women (6.7%) were parasitemic at recruitment but all were aparasitemic by 72 h. There were no differences in blood smear positivity rates between AZ-PQ and SP up to day 42 (0% versus 5.2%; relative risk [RR], 0.14 [95% confidence interval [CI], 0.01 to 2.58] [P = 0.18]; absolute risk reduction [ARR], 5.2% [95% CI, -1.3 to 11.6%]) and at the time of delivery (0% versus 8.7%; RR, 0.11 [95% CI, 0.01 to 2.01] [P = 0.14]; ARR, 8.7% [95% CI, -0.2 to 17.6%]). Of 92 women who were monitored to parturition, 89 (97%) delivered healthy babies; there were 3 stillbirths (SP, n = 1; AZ-PQ, n = 2 [twins]). There was a higher live birth weight (mean ± standard deviation) in the AZ-PQ group (3.13 ± 0.42 versus 2.88 ± 0.55 kg [P = 0.016]; mean difference, 0.25 kg [95% CI, 0.02 to 0.48 kg]). AZ-PQ is a promising candidate for IPTp.

KW - Azithromycin

KW - Efficacy

KW - Malaria

KW - Piperaquine

KW - Pregnancy

KW - Tolerability

UR - http://www.scopus.com/inward/record.url?scp=85072587338&partnerID=8YFLogxK

U2 - 10.1128/AAC.00302-19

DO - 10.1128/AAC.00302-19

M3 - Article

VL - 63

JO - Antimicrobial Agents and Chemotherapy

JF - Antimicrobial Agents and Chemotherapy

SN - 0066-4804

IS - 10

M1 - e00302-19

ER -