Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR202004580322097 Date of Approval: 16/04/2020
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Azithromycin-Prophylactic Labour Use Study ( A-PLUS)
Official scientific title Prevention of maternal and neonatal death/infections with a single oral dose of Azithromycin in women in labor (in low- and middle-income countries): a Randomized Controlled Trial
Brief summary describing the background and objectives of the trial The purpose of the A-PLUS study is to learn whether an antibiotic, called azithromycin, given by mouth to pregnant women during labor can reduce the risk of infection for the woman and her baby. A total of 34,000 women will be enrolled in this study from eight sites in sub-Saharan Africa, South Asia, and Latin America. The target population are pregnant women of legal age of consent who labor with one or more live fetuses and a pregnancy of ≥28 weeks, plan to deliver vaginally in a health facility, have no known infections that require antibiotics, have no known problems taking azithromycin or similar antibiotics (such as amoxicillin), and have not used azithromycin, erythromycin, or similar antibiotic in the past 3 days. 1.2 Primary Specific Aims To test the effectiveness of a single dose of prophylactic intrapartum azithromycin compared to placebo in reducing the risk of the composite outcome of maternal death or sepsis. To separately test the effectiveness of a single oral dose of intrapartum azithromycin prophylaxis (2 g) compared to placebo in reducing the risk of the composite outcome of intrapartum/neonatal death or sepsis. Both groups will receive the routine or usual care provided at the facility during and after labor. This will be ensured through training of all nurses on maternal and newborn care using the National guidelines and protocols as provided for by the Ministry of Health viz Basic Paediatric Protocols 2016, National Guidelines for Quality Obstetrics and Perinatal Care and National Guidelines on Essential Newborn Care. 1.3 Secondary Specific Aims The single dose of intrapartum azithromycin prophylaxis (2 g) will be compared to placebo to accomplish the following secondary aims: • Main Secondary Aim for Women at High Risk for Infection Cohort: a. To evaluate whether the risk of maternal death or sepsis differs among laboring women with and without high-risk for infection (high risk is defined as women with prolonged labor [≥18 hours] and/or pr
Type of trial RCT
Acronym (If the trial has an acronym then please provide) APLUS
Disease(s) or condition(s) being studied Infections and Infestations,maternal and newborn infections ,Obstetrics and Gynecology,Paediatrics
Sub-Disease(s) or condition(s) being studied maternal and newborn health,maternal and newborn infections
Purpose of the trial Prevention
Anticipated trial start date 01/04/2020
Actual trial start date 01/04/2020
Anticipated date of last follow up 15/04/2023
Actual Last follow-up date 15/12/2023
Anticipated target sample size (number of participants) 4250
Actual target sample size (number of participants) 4250
Recruitment status Recruiting
Publication URL https://globalnetwork.azurewebsites.net
Secondary Ids Issuing authority/Trial register
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Parallel: different groups receive different interventions at same time during study Randomised Simple randomization using a randomization table created by a computer software program Allocation was determined by the holder of the sequence who is situated off site Masking/blinding used Care giver/Provider,Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Azithromycin Single dose 2 grams once 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 vs. placebo. We will design the placebo with the assistance of a reputable pharmacy/pharmaceutical company, using identical capsules or pills containing azithromycin 2 g or a matching placebo (non-antimicrobial agent) to accomplish masking. All of the participants’ obstetric care will be similar for all in both arms and consist of the routinely available care at each center. 2125
Control Group Placebo Single dose 2 grams once 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 vs. placebo. We will design the placebo with the assistance of a reputable pharmacy/pharmaceutical company, using identical capsules or pills containing azithromycin 2 g or a matching placebo (non-antimicrobial agent) to accomplish masking. All of the participants’ obstetric care will be similar for all in both arms and consist of the routinely available care at each center. 2125 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
• 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 a fetal heart rate by Doptone prior to randomization. • Have provided written informed consent at gestation 28 weeks or beyond during antenatal care or home visits by the study field staff. However, verbal re-confirmation will be done at the time of randomization]. • Non-emancipated minors. • 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 by the pregnant woman or documented in a recent or any medical record. • Any use of azithromycin, erythromycin, or other macrolide in the 3 days or less prior to randomization as established during the enrolment process through history taking. • Plan for cesarean delivery prior to randomization. • Preterm labor undergoing management with no immediate plan to proceed to delivery. • Advanced stage of labor of 10cm cervical dilatation and pushing or too distressed to understand, confirm, or give informed consent regardless of cervical dilation. • Any other medical conditions that may be considered a contraindication per the judgment of the site investigator • Previous randomization in the trial. Adult: 19 Year-44 Year,New born: 0 Day-1 Month 18 Year(s) 40 Year(s) Female
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 17/04/2019 MU MTRH Institutional Research and Ethics Committee
Ethics Committee Address
Street address City Postal code Country
3 30100 Eldoret 30100 Kenya
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome The primary outcomes are: • Maternal: Incidence of maternal death or sepsis within 6 weeks (42 days) post-delivery in intervention vs. placebo group. • Neonatal: Incidence of intrapartum/neonatal death or sepsis within 7 days and 4 weeks (28 days) post-delivery in intervention vs. placebo group. Day 0, 3, 7, 14, 28 and 42
Secondary Outcome 2.6 Other Maternal Outcomes a. Chorioamnionitis: Fever (>100.4°F/38°C on two occasions at least 30 minutes apart or ≥102°F/39°C on one occasion) in addition to one or more of the following: fetal tachycardia >160bpm, maternal tachycardia>100bpm, uterine tenderness, or purulent lochia prior to delivery. b. Endometritis: Fever (>100.4°F/38°C on two occasions at least 30 minutes apart or ≥102°F/39°C on one occasion) in addition to one or more of uterine tenderness or purulent lochia after delivery. c. Other infections:Wound infection refers to purulent infection (superficial or deep infection including necrotizing fasciitis) of a perineal wound or wound of a subsequent cesarean with or without fever and leading to prescription of antibiotics; abdominopelvic abscess is evidence of pus noted during open surgery, interventional aspiration or imaging; pneumonia refers to fever and clinical symptoms suggestive of lung infection including cough and tachypnea with or without radiological confirmation; pyelonephritis refers to fever, urinalysis/dip suggestive of infection and Costovertebral angle tenderness with or without confirmatory urine culture). d. Use of subsequent maternal antibiotic therapy after randomization to 6 weeks for any reason. e. Maternal initial hospital length of stay, defined as the time of admission until initial discharge (time may vary by site). f. Maternal readmissions within 6 weeks of delivery. g. Maternal admission to special care units. h. Maternal GI symptoms including nausea, vomiting, and diarrhea and other reported side effects. 2.7 Other Neonatal Outcomes a. Neonatal initial hospital length of stay, defined as time of delivery until initial discharge (time may vary by site). b. Neonatal readmissions within 6 weeks of delivery. c. Neonatal admission to special care units. d. Neonatal death due to sepsis using the Global Network algorithm for causes of death. e. Pyloric stenosis within 6 weeks of delivery, defined as clinical suspicion based on severe vomiting leading to death or surgical intervention (pyloromyotomy) as verified from medical records with or without radiological confirmation. Day 0, 3, 7, 14, 28 and 42
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
Kenya site 12 Eldoret 3 Nandi road Eldoret 30100 Kenya
FUNDING SOURCES
Name of source Street address City Postal code Country
Eunice Kennedy Shriver National Institute of Child Health and Human Development 9000 Rockville Pike Bethesda 20892 United States of America
Bill and Melinda Gates Foundation 500 Fifth Avenue North Seattle 98109 United States of America
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Primary Sponsor Eunice Kennedy Shriver National Institute of Child Health and Human Development 9000 Rockville Pike Bethesda 20892 United States of America Funding Agency
Secondary Sponsor Bill and Melinda Gates Foundation 500 Fifth Avenue North Seattle 98109 United States of America Charities/Societies/Foundation
COLLABORATORS
Name Street address City Postal code Country
Indiana University 420 University Blvd Indianapolis 46202 United States of America
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Fabian Esamai fesamai2007@gmail.com 254724400189 3 Nandi road
City Postal code Country Position/Affiliation
Eldoret 30100 Kenya Moi University
Role Name Email Phone Street address
Public Enquiries Amos Sagwe asagwe35@gmail.com 254725953026 3 Nandi road
City Postal code Country Position/Affiliation
Eldoret 30100 Kenya Moi University
Role Name Email Phone Street address
Scientific Enquiries Paul Nyongesa drpaulnyongesa@yahoo.com 254733788063 3 Nandi road
City Postal code Country Position/Affiliation
Eldoret 30100 Kenya Moi University
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
Yes Primary publication Study Protocol After 3 years As per funding agency policy and data coordinating center
URL Results Available Results Summary Result Posting Date First Journal Publication Date
gn.rti.org No
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information