Postpartum SepsisPhase 4NCT03248297

Antibiotic Prophlaxis for High-risk Laboring Women in Low Income Countries

A Phase 4 study testing Azithromycin and Azithromycin and amoxicillin in people with Postpartum Sepsis and Postpartum Endometritis, run by University of Alabama at Birmingham at 1 site in Cameroon.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study, performed over a course of 3 years in 5 collaborating hospitals in Cameroon, Africa, will randomize 750 women in labor with prolonged rupture of membranes ≥ 8 hours or prolonged labor ≥ 18 hours to identical oral regimens of 1 gram of azithromycin, 1 gram of azithromycin+2 grams of amoxicillin or placebo. Read more about this study

Who is it for?: Any age, women onlyHealthy volunteers can take part
Conditions the study is for: Postpartum Sepsis, Postpartum Endometritis, Postpartum Fever
What is being tested?: Azithromycin and Azithromycin and amoxicillin
Type of treatment: Pill or oral medicine
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 756 participants
Where: 1 siteCameroon
Study dates: 12 Jan 2018to 1 Oct 2020
Phase: Phase 4

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

Ages Any age
Women only
Healthy volunteers accepted
Child, Adult, Older adult

Who may be able to join

Women ≥ 37 weeks' viable singleton or twin gestation in labor planning a vaginal delivery with
Prolonged membrane rupture (≥8 hours) or
Prolonged labor (≥18 hours).

Who cannot join

Clinical chorioamnionitis or any other active bacterial infection (e.g. pyelonephritis, pneumonia, abscess) at time of randomization: because standard antibiotic therapy for these conditions may confound trial intervention.
Allergy to azithromycin or amoxicillin
Plan for cesarean delivery prior to enrollment
Fetal demise or major congenital anomaly: Major congenital anomalies may confound assessment of neonatal outcomes and every attempt will be made up front to exclude them from randomization. However, some unrecognized fetal anomalies may inevitably be randomized. These will not be excluded post-randomization from the primary (maternal outcome) analysis; they will be taken into consideration in the secondary analyses of neonatal outcomes.

Trial locations and contacts

1 site in 1 country.

Cameroon1 site

Cameroon Baptist Convention Health Services
Bamenda

Other trials in Cameroon

About this study

Official title: Azithromycin With or Without Amoxicillin to Prevent Peripartum Infection and Sepsis in Laboring High-risk Women: 3-Arm RCT

Read the detailed description

This 3-arm study is a large randomized clinical trial designed to evaluate the comparative effectiveness and safety of single dose oral azithromycin or combined azithromycin+amoxicillin compared to placebo for the prevention of peripartum infections and sepsis in laboring women. We have previously shown the effectiveness of azithromycin for extended spectrum antibiotic prophylaxis in addition to the standard cephalosporin alone for reduction of post-cesarean infections. In LICs, the fraction of maternal infection and sepsis from cesarean delivery is minimal. Therefore, it is necessary to evaluate strategies aimed at reducing these morbidities in women who have vaginal births. There is an increased risk of infection in women who have prolonged labor or prolonged rupture of membranes. Drawing from our findings with azithromycin-based extended antibiotic prophylaxis for cesarean delivery, we propose to adapt the intervention and evaluate a single oral dose of azithromycin (with or without oral amoxicillin) to prevent maternal peripartum infection and sepsis. This study, performed over a course of 3 years in 5 collaborating hospitals in Cameroon, Africa, will randomize 750 women in labor with prolonged rupture of membranes ≥ 8 hours or prolonged labor ≥18 hours to 1 gram of oral azithromycin, 1 gram of azithromycin+2 grams of amoxicillin, compared to usual care (placebo). Women will be followed to ascertain maternal infectious outcomes and perinatal outcomes.

Conditions: Postpartum Sepsis, Postpartum Endometritis, Postpartum Fever
Being tested: Azithromycin, Azithromycin and amoxicillin, Placebo
Medical subject headings: Puerperal Infection

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

AzithromycinDrug
Azithromycin tablet
Azithromycin and amoxicillinDrug
Also called azithromycin, amoxicillin
azithromycin and amoxicillin
PlaceboDrug
Placebo tablet

Study groups in NCT03248297
Study group	Role	What they receive
Azithromycin and amoxicillin placebo	Experimental	Patients in this arm will receive 1 gram oral azithromycin as a single dose and amoxicillin placebo. Receives: Drug: Azithromycin; Drug: Placebo
Azithromycin + amoxicillin	Experimental	Patients in this arm will receive 1 gram oral azithromycin and 2 grams oral amoxicillin in a single dose. Receives: Drug: Azithromycin and amoxicillin
Usual Care	Placebo comparator	This arm will consist of routine care at the clinical sites (which is usually no antibiotic). They will receive placebo (for azithromycin) and placebo (for amoxicillin) Receives: Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

Number of Participants Who Experienced Composite Peripartum Infection or Death
Maternal peripartum infection including chorioamnionitis, endometritis, wound infection/abscess, sepsis, and death
Measured: Up to 6 weeks after delivery

Secondary outcomes (11)

Number of Participants Who Experienced Pyelonephritis
Other Infections
Measured: Up to hospital discharge
Number of Participants Who Experienced Breast Infection
Other infections
Measured: Up to 6 weeks after delivery
Number of Participants Who Experienced Other Infection
Includes Hepatitis B, thyroid infection, vaginal infection, viral infection, leg cellulitis, unknown abdominal infection,malaria
Measured: up to 6 weeks after delivery
Number of Participants Who Experienced Fever
Any fever higher than 38C
Measured: up to 6 weeks after delivery
Number of Participants Who Experienced Hypothermia
Any hypothermia less than 36C
Measured: up to 6 weeks after delivery
Number of Participants Who Needed PP Antibiotic
Any postpartum antibiotic
Measured: up to 6 weeks after delivery
Number of Participants Who Experienced Transfusion
Blood transfusion
Measured: up to 6 weeks after delivery
Number of Participants Who Experienced Stillbirth
Any stillbirth
Measured: delivery
Length of Stay
Length of stay in days
Measured: up to 6 weeks postpartum
Number of Participants Who Experienced a Clinic Visit
Clinic visit after discharge
Measured: up to 6 weeks after delivery
Number of Participants Who Experienced a Maternal Readmission
Maternal readmission
Measured: up to 6 weeks after delivery

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

12 Jan 20181 Oct 2020

First posted14 Aug 2017
Study start12 Jan 2018
Primary completion15 May 2020
Study completion1 Oct 2020

Resources

Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
Publications (5)Papers the sponsor has linked to this study.
Other trials for Postpartum SepsisStudies of the same condition, open and under way.
More trials run by University of Alabama at BirminghamThe sponsor's other registered studies.
What the trial phases meanHow a treatment moves from first tests in people to approval.

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design

Study type: Interventional
Phase: Phase 4
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Model description: Randomized Controlled Trial
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 756 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT03248297
Sponsor's protocol ID: CHI UAB MISP # 54628
Status last verified: Mar 2022
First submitted: 25 Jul 2017
Last updated: 18 Jul 2022
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: No
FDA-regulated device: No
Individual data sharing: No

Publications

Mangram AJ, Horan TC, Pearson ML, Silver LC, Jarvis WR. Guideline for Prevention of Surgical Site Infection, 1999. Centers for Disease Control and Prevention (CDC) Hospital Infection Control Practices Advisory Committee. Am J Infect Control. 1999 Apr;27(2):97-132; quiz 133-4; discussion 96.
PubMed 10196487
ASHP Therapeutic Guidelines on Antimicrobial Prophylaxis in Surgery. American Society of Health-System Pharmacists. Am J Health Syst Pharm. 1999 Sep 15;56(18):1839-88. doi: 10.1093/ajhp/56.18.1839. No abstract available.
PubMed 10511234
Tita ATN, Boggess K, Saade G. Adjunctive Azithromycin Prophylaxis for Cesarean Delivery. N Engl J Med. 2017 Jan 12;376(2):182. doi: 10.1056/NEJMc1614626. No abstract available.
PubMed 28076707
WHO. WHO recommendations for prevention and treatment of maternal peripartum infections. Sept 2015 http://www.who.int/reproductivehealth/publications/maternal_perinatal_health/peripartum-infections-guidelines/en/
Subramaniam A, Ye Y, Mbah R, Mbunwe DM, Pekwarake S, Bunwi EY, Fondzeyuf A, Ngong MG, Dionne-Odom J, Harper LM, Jauk VC, Carlo WA, Halle-Ekane G, Szychowski JM, Tih P, Tita AT. Single Dose of Oral Azithromycin With or Without Amoxicillin to Prevent Peripartum Infection in Laboring, High-Risk Women in Cameroon: A Randomized Controlled Trial. Obstet Gynecol. 2021 Nov 1;138(5):703-713. doi: 10.1097/AOG.0000000000004565.
PubMed 34619734