Study Results
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Recruitment Status
COMPLETED
Clinical Phase
PHASE3
Total Enrollment
58747 participants
Study Classification
INTERVENTIONAL
Study Start Date
2020-09-01
Study Completion Date
2022-09-30
Brief Summary
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Maternal and neonatal infections are among the most frequent causes of maternal and neonatal deaths, and current antibiotic strategies have not been effective in preventing many of these deaths. Recently, a randomized clinical trial conducted in a single site in The Gambia showed that treatment with oral dose of 2 g azithromycin vs. placebo for all women in labor reduced selected maternal and neonatal infections. However, it is unknown if this therapy reduces maternal and neonatal sepsis and mortality. The A-PLUS trial includes two primary hypotheses, a maternal hypothesis and a neonatal hypothesis. First, a single, prophylactic intrapartum oral dose of 2 g azithromycin given to women in labor will reduce maternal death or sepsis. Second, a single, prophylactic intrapartum oral dose of 2 g azithromycin given to women in labor will reduce intrapartum/neonatal death or sepsis.
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Detailed Description
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The A-PLUS Trial is a randomized, placebo-controlled, parallel multicenter clinical trial. The study intervention is a single, prophylactic intrapartum oral dose of 2 g azithromycin, with a comparison with a single intrapartum oral dose of an identical appearing placebo. For the A-PLUS randomized control trial (RCT), a total of 34,000 laboring women from eight research sites in sub-Saharan Africa, South Asia, and Latin America will be randomized with one-to-one ratio to intervention/placebo. In response to the global coronavirus pandemic, research sites will also collect data on COVID-19 signs/symptoms, diagnosis, and treatment in order to estimate the incidence of infection and evaluate the impact of the pandemic on the target population.
Prior to the initiation of the A-PLUS RCT, research sites will conduct an observational pilot study using the RCT's planned infrastructure in order to characterize the current practices at participating research facilities and optimize the identification of suspected infection for the RCT. The information obtained in the pilot study will be used to validate estimates of intrapartum deaths, maternal sepsis, and neonatal sepsis used in the sample size calculations for the RCT. Finally, the pilot study will allow the research sites to inventory and upgrade local capacity to conduct routine cultures during the RCT.
A maximum of 16,000 women, separate from the sample for the main trial, will be enrolled in the pilot, across all eight research sites, with no more than 2000 women enrolled at any individual site. Research sites will be eligible to transition to the RCT when a minimum of 600 participants have been enrolled in the pilot study with evidence of (a) high rates of follow-up; (2) acceptable data quality and completeness; and (3) there are no concerns about identification and reporting of infection.
Given the clinical benefits of intrapartum azithromycin so far reported in two trials and the likelihood that it may become the usual practice if the investigator's large RCT confirms the reported benefits, it is important to monitor antibiotic resistance to determine the safety of azithromycin prophylaxis. Therefore, the RCT will also include an ancillary study (referred to as the antimicrobial resistance (AMR) sub-study) to monitor antimicrobial resistance and maternal and newborn microbiome effects of the single dose of prophylactic azithromycin using the following methodology
1. For all mothers enrolled in the RCT and their infants:
a. Routine clinical monitoring at baseline and three post-partum time points (3 days, 7 days, and 42 days), with culture and sensitivity testing in cases of suspected bacterial infections;
2. Among a subset of 1000 randomly selected maternal-infant dyads:
1. Serial susceptibility monitoring of antimicrobial resistance patterns (including azithromycin resistance) from selected maternal and newborn flora through culture and sensitivity testing. Serial monitoring will be conducted at baseline and three post-partum time points (1 week, 6 weeks, and 3 months).
2. Serial microbiome collection and storage of specimens for future testing to monitor maternal and newborn microbiome status of selected sites.
Prior to the initiation of the A-PLUS RCT, research sites will conduct an observational pilot study using the RCT's planned infrastructure in order to characterize the current practices at participating research facilities and optimize the identification of suspected infection for the RCT. The information obtained in the pilot study will be used to validate estimates of intrapartum deaths, maternal sepsis, and neonatal sepsis used in the sample size calculations for the RCT. Finally, the pilot study will allow the research sites to inventory and upgrade local capacity to conduct routine cultures during the RCT.
A maximum of 16,000 women, separate from the sample for the main trial, will be enrolled in the pilot, across all eight research sites, with no more than 2000 women enrolled at any individual site. Research sites will be eligible to transition to the RCT when a minimum of 600 participants have been enrolled in the pilot study with evidence of (a) high rates of follow-up; (2) acceptable data quality and completeness; and (3) there are no concerns about identification and reporting of infection.
Given the clinical benefits of intrapartum azithromycin so far reported in two trials and the likelihood that it may become the usual practice if the investigator's large RCT confirms the reported benefits, it is important to monitor antibiotic resistance to determine the safety of azithromycin prophylaxis. Therefore, the RCT will also include an ancillary study (referred to as the antimicrobial resistance (AMR) sub-study) to monitor antimicrobial resistance and maternal and newborn microbiome effects of the single dose of prophylactic azithromycin using the following methodology
1. For all mothers enrolled in the RCT and their infants:
a. Routine clinical monitoring at baseline and three post-partum time points (3 days, 7 days, and 42 days), with culture and sensitivity testing in cases of suspected bacterial infections;
2. Among a subset of 1000 randomly selected maternal-infant dyads:
1. Serial susceptibility monitoring of antimicrobial resistance patterns (including azithromycin resistance) from selected maternal and newborn flora through culture and sensitivity testing. Serial monitoring will be conducted at baseline and three post-partum time points (1 week, 6 weeks, and 3 months).
2. Serial microbiome collection and storage of specimens for future testing to monitor maternal and newborn microbiome status of selected sites.
Conditions
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Maternal Death
Maternal Infections Affecting Fetus or Newborn
Neonatal SEPSIS
Maternal Sepsis During Labor
Neonatal Death
Postpartum Sepsis
Study Design
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Allocation Method
RANDOMIZED
Intervention Model
PARALLEL
Randomized, placebo-controlled, parallel multicenter clinical trial. Women in labor will be randomized with one-to-one ratio to intervention/placebo.
Primary Study Purpose
PREVENTION
Blinding Strategy
TRIPLE
Participants
Caregivers
Investigators
Both the azithromycin and placebo will be procured from the same manufacturer. The packaging will be standardized across sites and will be labeled as: "Azithromycin 2 g or Placebo", with the expiration data and a unique identifier.
Clinical and research staff as well as the women will be masked to treatment status unless there is a serious adverse event potentially related to the treatment modality that requires unmasking for safety reasons. There will be one pharmacist at each site who will monitor randomization, drug supply, and safety. If concerns about randomization or participant safety are identified, the data coordinating center will authorize and instruct the study pharmacist to apply un-masking procedures.
Clinical and research staff as well as the women will be masked to treatment status unless there is a serious adverse event potentially related to the treatment modality that requires unmasking for safety reasons. There will be one pharmacist at each site who will monitor randomization, drug supply, and safety. If concerns about randomization or participant safety are identified, the data coordinating center will authorize and instruct the study pharmacist to apply un-masking procedures.
Study Groups
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Intervention
The study intervention is a single 2 g dose of directly observed oral azithromycin.
Group Type
EXPERIMENTAL
Azithromycin
Intervention Type
DRUG
The study intervention is a single 2 g dose of directly observed oral azithromycin, to be administered as four 500 mg pills or tablets directly after randomization. By random allocation, participants will receive 2 g of oral azithromycin.
Placebo
By random allocation, participants will receive four oral placebo pills containing a non-antimicrobial agent directly after randomization.
Group Type
PLACEBO_COMPARATOR
Placebo
Intervention Type
DRUG
Identical appearing placebo, administered as a single oral dose directly after randomization.
Interventions
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Azithromycin
The study intervention is a single 2 g dose of directly observed oral azithromycin, to be administered as four 500 mg pills or tablets directly after randomization. By random allocation, participants will receive 2 g of oral azithromycin.
Intervention Type
DRUG
Placebo
Identical appearing placebo, administered as a single oral dose directly after randomization.
Intervention Type
DRUG
Eligibility Criteria
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Inclusion Criteria
* Pregnant women in labor ≥28 weeks Gestational Age (GA) (by best estimate) with a pregnancy with one or more live fetuses who plan to deliver vaginally in a facility.
* Admitted to health facility with clear plan for spontaneous or induced delivery.
* Live fetus must be confirmed via a fetal heart rate by Doptone prior to randomization.
* ≥18 years of age or minors 14-17 years of age in countries where married or pregnant minors (or their authorized representatives) are legally permitted to give consent.
* Have provided written informed consent.
* Pregnant women in labor ≥28 weeks GA (by best estimate) with a pregnancy with one or more live fetuses who plan to deliver vaginally in a facility.
* Admitted to health facility with clear plan for spontaneous or induced delivery.
* Live fetus must be confirmed via presence of a fetal heart rate prior to randomization.
* ≥18 years of age or minors 14-17 years of age in countries where married or pregnant minors (or their authorized representatives) are legally permitted to give consent.
* Have provided written informed consent \[Note: written informed consent may be obtained during antenatal care, but verbal re-confirmation may be needed (per local regulations) at the time of randomization\].
* Admitted to health facility with clear plan for spontaneous or induced delivery.
* Live fetus must be confirmed via a fetal heart rate by Doptone prior to randomization.
* ≥18 years of age or minors 14-17 years of age in countries where married or pregnant minors (or their authorized representatives) are legally permitted to give consent.
* Have provided written informed consent.
* Pregnant women in labor ≥28 weeks GA (by best estimate) with a pregnancy with one or more live fetuses who plan to deliver vaginally in a facility.
* Admitted to health facility with clear plan for spontaneous or induced delivery.
* Live fetus must be confirmed via presence of a fetal heart rate prior to randomization.
* ≥18 years of age or minors 14-17 years of age in countries where married or pregnant minors (or their authorized representatives) are legally permitted to give consent.
* Have provided written informed consent \[Note: written informed consent may be obtained during antenatal care, but verbal re-confirmation may be needed (per local regulations) at the time of randomization\].
Exclusion Criteria
* Non-emancipated minors (as per local regulations)
* Evidence of chorioamnionitis or other infection requiring antibiotic therapy at time of eligibility (however, women given single prophylactic antibiotics with no plans to continue after delivery should not be excluded).
* Arrhythmia or known history of cardiomyopathy.
* Allergy to azithromycin or other macrolides that is self-reported or documented in the medical record.
* Any use of azithromycin, erythromycin, or other macrolide in the 3 days or less prior to randomization.
* Plan for cesarean delivery prior to randomization.
* Preterm labor undergoing management with no immediate plan to proceed to delivery.
* Advanced stage of labor (\>6 cm or 10 cm cervical dilation per local standards) and pushing or too distressed to understand, confirm, or give informed consent regardless of cervical dilation.
* Are not capable of giving consent due to other health problems such as obstetric emergencies (for example, antepartum hemorrhage) or mental disorder.
* Any other medical conditions that may be considered a contraindication per the judgment of the site investigator.
* Previous randomization in the trial.
* Evidence of chorioamnionitis or other infection requiring antibiotic therapy at time of eligibility (however, women given single prophylactic antibiotics with no plans to continue after delivery should not be excluded).
* Arrhythmia or known history of cardiomyopathy.
* Allergy to azithromycin or other macrolides that is self-reported or documented in the medical record.
* Any use of azithromycin, erythromycin, or other macrolide in the 3 days or less prior to randomization.
* Plan for cesarean delivery prior to randomization.
* Preterm labor undergoing management with no immediate plan to proceed to delivery.
* Advanced stage of labor (\>6 cm or 10 cm cervical dilation per local standards) and pushing or too distressed to understand, confirm, or give informed consent regardless of cervical dilation.
* Are not capable of giving consent due to other health problems such as obstetric emergencies (for example, antepartum hemorrhage) or mental disorder.
* Any other medical conditions that may be considered a contraindication per the judgment of the site investigator.
* Previous randomization in the trial.
Minimum Eligible Age
18 Years
Maximum Eligible Age
45 Years
Eligible Sex
FEMALE
Accepts Healthy Volunteers
Yes
Sponsors
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University of Alabama at Birmingham
OTHER
Sponsor Role
collaborator
University Teaching Hospital, Lusaka, Zambia
OTHER
Sponsor Role
collaborator
University of North Carolina, Chapel Hill
OTHER
Sponsor Role
collaborator
Kinshasa School of Public Health
OTHER
Sponsor Role
collaborator
University of Colorado, Denver
OTHER
Sponsor Role
collaborator
Institute of Nutrition of Central America and Panama
OTHER
Sponsor Role
collaborator
University of Virginia
OTHER
Sponsor Role
collaborator
International Centre for Diarrhoeal Disease Research, Bangladesh
OTHER
Sponsor Role
collaborator
Thomas Jefferson University
OTHER
Sponsor Role
collaborator
Columbia University
OTHER
Sponsor Role
collaborator
Aga Khan University
OTHER
Sponsor Role
collaborator
Boston University
OTHER
Sponsor Role
collaborator
Lata Medical Research Foundation, Nagpur
OTHER
Sponsor Role
collaborator
Indiana University School of Medicine
OTHER
Sponsor Role
collaborator
Moi Univeristy
OTHER
Sponsor Role
collaborator
RTI International
OTHER
Sponsor Role
collaborator
Bill and Melinda Gates Foundation
OTHER
Sponsor Role
collaborator
Jawaharlal Nehru Medical College
OTHER
Sponsor Role
collaborator
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
NIH
Sponsor Role
collaborator
NICHD Global Network for Women's and Children's Health
NETWORK
Sponsor Role
lead
Responsible Party
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Responsibility Role
SPONSOR
Principal Investigators
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Marion Koso-Thomas, MD
Role: STUDY_DIRECTOR
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Locations
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ICDDRB
Dhaka, , Bangladesh
Site Status
Kinshasa School of Public Health
Kinshasa, , Democratic Republic of the Congo
Site Status
Institute for Nutrition of Central America and Panama (INCAP)
Guatemala City, , Guatemala
Site Status
Jawaharlal Nehru Medical College
Belagām, , India
Site Status
Lata Medical Research Foundation
Nagpur, , India
Site Status
Moi University School of Medicine
Eldoret, , Kenya
Site Status
The Aga Khan University
Karachi, , Pakistan
Site Status
University Teaching Hospital
Lusaka, , Zambia
Site Status
Countries
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Bangladesh
Democratic Republic of the Congo
Guatemala
India
Kenya
Pakistan
Zambia
References
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WHO Recommendations for Prevention and Treatment of Maternal Peripartum Infections. Geneva: World Health Organization; 2015. Available from http://www.ncbi.nlm.nih.gov/books/NBK327079/
Reference Type
BACKGROUND
Liu L, Oza S, Hogan D, Perin J, Rudan I, Lawn JE, Cousens S, Mathers C, Black RE. Global, regional, and national causes of child mortality in 2000-13, with projections to inform post-2015 priorities: an updated systematic analysis. Lancet. 2015 Jan 31;385(9966):430-40. doi: 10.1016/S0140-6736(14)61698-6. Epub 2014 Sep 30.
Reference Type
BACKGROUND
African Neonatal Sepsis Trial (AFRINEST) group; Tshefu A, Lokangaka A, Ngaima S, Engmann C, Esamai F, Gisore P, Ayede AI, Falade AG, Adejuyigbe EA, Anyabolu CH, Wammanda RD, Ejembi CL, Ogala WN, Gram L, Cousens S. Simplified antibiotic regimens compared with injectable procaine benzylpenicillin plus gentamicin for treatment of neonates and young infants with clinical signs of possible serious bacterial infection when referral is not possible: a randomised, open-label, equivalence trial. Lancet. 2015 May 2;385(9979):1767-1776. doi: 10.1016/S0140-6736(14)62284-4. Epub 2015 Apr 1.
Reference Type
BACKGROUND
Baqui AH, Saha SK, Ahmed AS, Shahidullah M, Quasem I, Roth DE, Samsuzzaman AK, Ahmed W, Tabib SM, Mitra DK, Begum N, Islam M, Mahmud A, Rahman MH, Moin MI, Mullany LC, Cousens S, El Arifeen S, Wall S, Brandes N, Santosham M, Black RE; Projahnmo Study Group in Bangladesh. Safety and efficacy of alternative antibiotic regimens compared with 7 day injectable procaine benzylpenicillin and gentamicin for outpatient treatment of neonates and young infants with clinical signs of severe infection when referral is not possible: a randomised, open-label, equivalence trial. Lancet Glob Health. 2015 May;3(5):e279-87. doi: 10.1016/S2214-109X(14)70347-X. Epub 2015 Apr 1.
Reference Type
BACKGROUND
Mir F, Nisar I, Tikmani SS, Baloch B, Shakoor S, Jehan F, Ahmed I, Cousens S, Zaidi AK. Simplified antibiotic regimens for treatment of clinical severe infection in the outpatient setting when referral is not possible for young infants in Pakistan (Simplified Antibiotic Therapy Trial [SATT]): a randomised, open-label, equivalence trial. Lancet Glob Health. 2017 Feb;5(2):e177-e185. doi: 10.1016/S2214-109X(16)30335-7. Epub 2016 Dec 15.
Reference Type
BACKGROUND
Zaidi AK, Tikmani SS, Sultana S, Baloch B, Kazi M, Rehman H, Karimi K, Jehan F, Ahmed I, Cousens S. Simplified antibiotic regimens for the management of clinically diagnosed severe infections in newborns and young infants in first-level facilities in Karachi, Pakistan: study design for an outpatient randomized controlled equivalence trial. Pediatr Infect Dis J. 2013 Sep;32 Suppl 1(Suppl 1 Innovative Treatment Regimens for Severe Infections in Young Infants):S19-25. doi: 10.1097/INF.0b013e31829ff7aa.
Reference Type
BACKGROUND
Gibbs RS. Clinical risk factors for puerperal infection. Obstet Gynecol. 1980 May;55(5 Suppl):178S-184S. doi: 10.1097/00006250-198003001-00045.
Reference Type
BACKGROUND
World Health Organization. (2015). WHO Statement on Caesarean Section Rates. Retrieved August 22, 2018, from http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/cs-statement/en/
Reference Type
BACKGROUND
Mackeen AD, Packard RE, Ota E, Berghella V, Baxter JK. Timing of intravenous prophylactic antibiotics for preventing postpartum infectious morbidity in women undergoing cesarean delivery. Cochrane Database Syst Rev. 2014 Dec 5;2014(12):CD009516. doi: 10.1002/14651858.CD009516.pub2.
Reference Type
BACKGROUND
Smaill FM, Grivell RM. Antibiotic prophylaxis versus no prophylaxis for preventing infection after cesarean section. Cochrane Database Syst Rev. 2014 Oct 28;2014(10):CD007482. doi: 10.1002/14651858.CD007482.pub3.
Reference Type
BACKGROUND
Gyte GM, Dou L, Vazquez JC. Different classes of antibiotics given to women routinely for preventing infection at caesarean section. Cochrane Database Syst Rev. 2014 Nov 17;2014(11):CD008726. doi: 10.1002/14651858.CD008726.pub2.
Reference Type
BACKGROUND
Tita ATN, Rouse DJ, Blackwell S, Saade GR, Spong CY, Andrews WW. Emerging concepts in antibiotic prophylaxis for cesarean delivery: a systematic review. Obstet Gynecol. 2009 Mar;113(3):675-682. doi: 10.1097/AOG.0b013e318197c3b6.
Reference Type
BACKGROUND
Tita AT, Szychowski JM, Boggess K, Saade G, Longo S, Clark E, Esplin S, Cleary K, Wapner R, Letson K, Owens M, Abramovici A, Ambalavanan N, Cutter G, Andrews W; C/SOAP Trial Consortium. Adjunctive Azithromycin Prophylaxis for Cesarean Delivery. N Engl J Med. 2016 Sep 29;375(13):1231-41. doi: 10.1056/NEJMoa1602044.
Reference Type
BACKGROUND
Oluwalana C, Camara B, Bottomley C, Goodier S, Bojang A, Kampmann B, Ceesay S, D'Alessandro U, Roca A. Azithromycin in Labor Lowers Clinical Infections in Mothers and Newborns: A Double-Blind Trial. Pediatrics. 2017 Feb;139(2):e20162281. doi: 10.1542/peds.2016-2281.
Reference Type
BACKGROUND
World Health Organization. (2017). Statement on maternal sepsis. Retrieved Ausust 22, 2018, from http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/maternalsepsis-statement/en/
Reference Type
BACKGROUND
Reinhart K, Daniels R, Kissoon N, Machado FR, Schachter RD, Finfer S. Recognizing Sepsis as a Global Health Priority - A WHO Resolution. N Engl J Med. 2017 Aug 3;377(5):414-417. doi: 10.1056/NEJMp1707170. Epub 2017 Jun 28. No abstract available.
Reference Type
BACKGROUND
van Dillen J, Zwart J, Schutte J, van Roosmalen J. Maternal sepsis: epidemiology, etiology and outcome. Curr Opin Infect Dis. 2010 Jun;23(3):249-54. doi: 10.1097/QCO.0b013e328339257c.
Reference Type
BACKGROUND
Roca A, Oluwalana C, Bojang A, Camara B, Kampmann B, Bailey R, Demba A, Bottomley C, D'Alessandro U. Oral azithromycin given during labour decreases bacterial carriage in the mothers and their offspring: a double-blind randomized trial. Clin Microbiol Infect. 2016 Jun;22(6):565.e1-9. doi: 10.1016/j.cmi.2016.03.005. Epub 2016 Mar 26.
Reference Type
BACKGROUND
Harper LM, Kilgore M, Szychowski JM, Andrews WW, Tita ATN. Economic Evaluation of Adjunctive Azithromycin Prophylaxis for Cesarean Delivery. Obstet Gynecol. 2017 Aug;130(2):328-334. doi: 10.1097/AOG.0000000000002129.
Reference Type
BACKGROUND
Andrews WW, Hauth JC, Cliver SP, Savage K, Goldenberg RL. Randomized clinical trial of extended spectrum antibiotic prophylaxis with coverage for Ureaplasma urealyticum to reduce post-cesarean delivery endometritis. Obstet Gynecol. 2003 Jun;101(6):1183-9. doi: 10.1016/s0029-7844(03)00016-4.
Reference Type
BACKGROUND
Tita AT, Hauth JC, Grimes A, Owen J, Stamm AM, Andrews WW. Decreasing incidence of postcesarean endometritis with extended-spectrum antibiotic prophylaxis. Obstet Gynecol. 2008 Jan;111(1):51-6. doi: 10.1097/01.AOG.0000295868.43851.39.
Reference Type
BACKGROUND
Tita AT, Owen J, Stamm AM, Grimes A, Hauth JC, Andrews WW. Impact of extended-spectrum antibiotic prophylaxis on incidence of postcesarean surgical wound infection. Am J Obstet Gynecol. 2008 Sep;199(3):303.e1-3. doi: 10.1016/j.ajog.2008.06.068.
Reference Type
BACKGROUND
Watts DH, Eschenbach DA, Kenny GE. Early postpartum endometritis: the role of bacteria, genital mycoplasmas, and Chlamydia trachomatis. Obstet Gynecol. 1989 Jan;73(1):52-60.
Reference Type
BACKGROUND
Hoyme UB, Kiviat N, Eschenbach DA. Microbiology and treatment of late postpartum endometritis. Obstet Gynecol. 1986 Aug;68(2):226-32.
Reference Type
BACKGROUND
Emmons SL, Krohn M, Jackson M, Eschenbach DA. Development of wound infections among women undergoing cesarean section. Obstet Gynecol. 1988 Oct;72(4):559-64.
Reference Type
BACKGROUND
Roberts S, Maccato M, Faro S, Pinell P. The microbiology of post-cesarean wound morbidity. Obstet Gynecol. 1993 Mar;81(3):383-6.
Reference Type
BACKGROUND
Rosene K, Eschenbach DA, Tompkins LS, Kenny GE, Watkins H. Polymicrobial early postpartum endometritis with facultative and anaerobic bacteria, genital mycoplasmas, and Chlamydia trachomatis: treatment with piperacillin or cefoxitin. J Infect Dis. 1986 Jun;153(6):1028-37. doi: 10.1093/infdis/153.6.1028.
Reference Type
BACKGROUND
Andrews WW, Shah SR, Goldenberg RL, Cliver SP, Hauth JC, Cassell GH. Association of post-cesarean delivery endometritis with colonization of the chorioamnion by Ureaplasma urealyticum. Obstet Gynecol. 1995 Apr;85(4):509-14. doi: 10.1016/0029-7844(94)00436-H.
Reference Type
BACKGROUND
Keski-Nisula L, Kirkinen P, Katila ML, Ollikainen M, Suonio S, Saarikoski S. Amniotic fluid U. urealyticum colonization: significance for maternal peripartal infections at term. Am J Perinatol. 1997 Mar;14(3):151-6. doi: 10.1055/s-2007-994117.
Reference Type
BACKGROUND
Yoon BH, Romero R, Park JS, Chang JW, Kim YA, Kim JC, Kim KS. Microbial invasion of the amniotic cavity with Ureaplasma urealyticum is associated with a robust host response in fetal, amniotic, and maternal compartments. Am J Obstet Gynecol. 1998 Nov;179(5):1254-60. doi: 10.1016/s0002-9378(98)70142-5.
Reference Type
BACKGROUND
Ledger WJ. Prophylactic antibiotics in obstetrics-gynecology: a current asset, a future liability? Expert Rev Anti Infect Ther. 2006 Dec;4(6):957-64. doi: 10.1586/14787210.4.6.957.
Reference Type
BACKGROUND
Guideline: Managing Possible Serious Bacterial Infection in Young Infants When Referral Is Not Feasible. Geneva: World Health Organization; 2015. Available from http://www.ncbi.nlm.nih.gov/books/NBK321136/
Reference Type
BACKGROUND
Sutton AL, Acosta EP, Larson KB, Kerstner-Wood CD, Tita AT, Biggio JR. Perinatal pharmacokinetics of azithromycin for cesarean prophylaxis. Am J Obstet Gynecol. 2015 Jun;212(6):812.e1-6. doi: 10.1016/j.ajog.2015.01.015. Epub 2015 Jan 13.
Reference Type
BACKGROUND
Eberly MD, Eide MB, Thompson JL, Nylund CM. Azithromycin in early infancy and pyloric stenosis. Pediatrics. 2015 Mar;135(3):483-8. doi: 10.1542/peds.2014-2026.
Reference Type
BACKGROUND
Ray WA, Murray KT, Hall K, Arbogast PG, Stein CM. Azithromycin and the risk of cardiovascular death. N Engl J Med. 2012 May 17;366(20):1881-90. doi: 10.1056/NEJMoa1003833.
Reference Type
BACKGROUND
Svanstrom H, Pasternak B, Hviid A. Use of azithromycin and death from cardiovascular causes. N Engl J Med. 2013 May 2;368(18):1704-12. doi: 10.1056/NEJMoa1300799.
Reference Type
BACKGROUND
Hoffman MK, Goudar SS, Kodkany BS, Goco N, Koso-Thomas M, Miodovnik M, McClure EM, Wallace DD, Hemingway-Foday JJ, Tshefu A, Lokangaka A, Bose CL, Chomba E, Mwenechanya M, Carlo WA, Garces A, Krebs NF, Hambidge KM, Saleem S, Goldenberg RL, Patel A, Hibberd PL, Esamai F, Liechty EA, Silver R, Derman RJ. A description of the methods of the aspirin supplementation for pregnancy indicated risk reduction in nulliparas (ASPIRIN) study. BMC Pregnancy Childbirth. 2017 May 3;17(1):135. doi: 10.1186/s12884-017-1312-x.
Reference Type
BACKGROUND
Goldenberg RL, Saleem S, Ali S, Moore JL, Lokangako A, Tshefu A, Mwenechanya M, Chomba E, Garces A, Figueroa L, Goudar S, Kodkany B, Patel A, Esamai F, Nsyonge P, Harrison MS, Bauserman M, Bose CL, Krebs NF, Hambidge KM, Derman RJ, Hibberd PL, Liechty EA, Wallace DD, Belizan JM, Miodovnik M, Koso-Thomas M, Carlo WA, Jobe AH, McClure EM. Maternal near miss in low-resource areas. Int J Gynaecol Obstet. 2017 Sep;138(3):347-355. doi: 10.1002/ijgo.12219. Epub 2017 Jun 13.
Reference Type
BACKGROUND
Bonet M, Souza JP, Abalos E, Fawole B, Knight M, Kouanda S, Lumbiganon P, Nabhan A, Nadisauskiene R, Brizuela V, Metin Gulmezoglu A. The global maternal sepsis study and awareness campaign (GLOSS): study protocol. Reprod Health. 2018 Jan 30;15(1):16. doi: 10.1186/s12978-017-0437-8.
Reference Type
BACKGROUND
Albright CM, Has P, Rouse DJ, Hughes BL. Internal Validation of the Sepsis in Obstetrics Score to Identify Risk of Morbidity From Sepsis in Pregnancy. Obstet Gynecol. 2017 Oct;130(4):747-755. doi: 10.1097/AOG.0000000000002260.
Reference Type
BACKGROUND
Bowyer L, Robinson HL, Barrett H, Crozier TM, Giles M, Idel I, Lowe S, Lust K, Marnoch CA, Morton MR, Said J, Wong M, Makris A. SOMANZ guidelines for the investigation and management sepsis in pregnancy. Aust N Z J Obstet Gynaecol. 2017 Oct;57(5):540-551. doi: 10.1111/ajo.12646. Epub 2017 Jul 3.
Reference Type
BACKGROUND
Carlo WA, Tita ATN, Moore JL, Mwenechanya M, Chomba E, Hemingway-Foday JJ, Kavi A, Metgud MC, Goudar SS, Derman RJ, Lokangaka A, Tshefu A, Bauserman M, Patterson JK, Shivkumar P, Waikar M, Patel A, Hibberd PL, Nyongesa P, Esamai F, Ekhaguere OA, Bucher S, Jessani S, Tikmani SS, Saleem S, Goldenberg RL, Billah SM, Lennox R, Haque R, Petri W, Mazariegos M, Krebs NF, Babineau DC, McClure EM, Koso-Thomas M; A-PLUS Trial Group. Effectiveness of intrapartum azithromycin to prevent infections in planned vaginal births in low-income and middle-income countries: a post-hoc analysis of data from a multicentre, randomised, double-blind, placebo-controlled trial. Lancet Glob Health. 2025 Apr;13(4):e689-e697. doi: 10.1016/S2214-109X(24)00562-X.
Reference Type
DERIVED
Patterson JK, Neuwahl S, Kirsch S, Moore JL, Tita ATN, Carlo WA, Lokangaka A, Tshefu A, Mwenechanya M, Chomba E, Kavi A, Metgud MC, Goudar SS, Derman RJ, Shivkumar P, Waikar M, Patel A, Hibberd PL, Nyongesa P, Esamai F, Ekhaguere OA, Bucher S, Jessani S, Tikmani SS, Saleem S, Wylie BJ, Goldenberg RL, Billah SM, Lennox R, Haque R, Petri WA, Mazariegos M, Krebs NF, Hemingway-Foday JJ, Babineau D, Koso-Thomas M, McClure EM, Bauserman M. Cost-effectiveness of intrapartum azithromycin to prevent maternal infection, sepsis, or death in low-income and middle-income countries: a modelling analysis of data from a randomised, multicentre, placebo-controlled trial. Lancet Glob Health. 2025 Apr;13(4):e679-e688. doi: 10.1016/S2214-109X(24)00517-5.
Reference Type
DERIVED
Hemingway-Foday J, Tita A, Chomba E, Mwenechanya M, Mweemba T, Nolen T, Lokangaka A, Tshefu Kitoto A, Lomendje G, Hibberd PL, Patel A, Das PK, Kurhe K, Goudar SS, Kavi A, Metgud M, Saleem S, Tikmani SS, Esamai F, Nyongesa P, Sagwe A, Figueroa L, Mazariegos M, Billah SM, Haque R, Shahjahan Siraj M, Goldenberg RL, Bauserman M, Bose C, Liechty EA, Ekhaguere OA, Krebs NF, Derman R, Petri WA, Koso-Thomas M, McClure E, Carlo WA. Prevention of maternal and neonatal death/infections with a single oral dose of azithromycin in women in labour in low-income and middle-income countries (A-PLUS): a study protocol for a multinational, randomised placebo-controlled clinical trial. BMJ Open. 2023 Aug 30;13(8):e068487. doi: 10.1136/bmjopen-2022-068487.
Reference Type
DERIVED
Tita ATN, Carlo WA, McClure EM, Mwenechanya M, Chomba E, Hemingway-Foday JJ, Kavi A, Metgud MC, Goudar SS, Derman R, Lokangaka A, Tshefu A, Bauserman M, Bose C, Shivkumar P, Waikar M, Patel A, Hibberd PL, Nyongesa P, Esamai F, Ekhaguere OA, Bucher S, Jessani S, Tikmani SS, Saleem S, Goldenberg RL, Billah SM, Lennox R, Haque R, Petri W, Figueroa L, Mazariegos M, Krebs NF, Moore JL, Nolen TL, Koso-Thomas M; A-PLUS Trial Group. Azithromycin to Prevent Sepsis or Death in Women Planning a Vaginal Birth. N Engl J Med. 2023 Mar 30;388(13):1161-1170. doi: 10.1056/NEJMoa2212111. Epub 2023 Feb 9.
Reference Type
DERIVED
Provided Documents
Download supplemental materials such as informed consent forms, study protocols, or participant manuals.
Document Type: Study Protocol, Statistical Analysis Plan, and Informed Consent Form
Other Identifiers
Review additional registry numbers or institutional identifiers associated with this trial.
CP Azithromycin
Identifier Type: -
Identifier Source: org_study_id
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