Comparison of Ceftriaxone/Azithromycin versus Amoxicillin/Azithromycin for Prophylaxis in Pregnant Women with Preterm Prelabor Rupture of Membranes at 22 to 33 Weeks' Gestation

The primary objective is to demonstrate the superiority of the ceftriaxone and azithromycin combination compared to the reference amoxicillin and azithromycin regimen regarding perinatal morbi-mortality in patients with preterm prelabor rupture of membranes between 22 and 33 weeks of gestation. The secondary objectives include evaluating the superiority of ceftriaxone over the reference combination on:

• Latency duration
• Maternal morbidity
• Neonatal minor morbidity

The sponsor did not provide information regarding the total number of participants. The study population consists of pregnant women presenting with preterm premature rupture of membranes (PPROM) between 22 and 33 weeks of gestation. Eligible participants include those with a singleton gestation and a live foetus at the time of randomization. Inclusion requires an age of 18 years or older, French language proficiency, and affiliation with a French social security regime or equivalent system. The diagnosis of PPROM must be confirmed through clinical history combined with physical examination or laboratory testing. All participants must be eligible for the standard antibiotic prophylaxis protocol at the inclusion center.

This randomized controlled trial is designed to evaluate the superiority of a ceftriaxone and azithromycin regimen compared to an amoxicillin and azithromycin regimen for prophylaxis in cases of preterm prelabor rupture of membranes occurring between 22 and 33 weeks of gestation. The study follows a Phase III methodology. The primary endpoint is a composite outcome comprising fetal death, neonatal death, or neonatal severe morbidity, such as mechanical ventilation, bronchopulmonary dysplasia, intraventricular haemorrhage, white matter injury, neonatal sepsis, necrotizing enterocolitis, or retinopathy of prematurity. Secondary outcomes include pregnancy duration, maternal infectious morbidity, and neonatal mild or moderate morbidity. The clinical trial is estimated to occur between July 2026 and November 2031.

The experimental treatment consists of ceftriaxone administered at a dose of 1 g via intravenous, subcutaneous, or intramuscular routes.

The comparator regimen involves the administration of amoxicillin at a dose of 3 g for oral use in combination with azithromycin at a dose of 500 mg for oral use.

The primary efficacy assessment is a composite outcome comprising fetal death, neonatal death, and/or neonatal severe morbidity. The criteria for neonatal severe morbidity include mechanical ventilation for at least 48 hours, severe bronchopulmonary dysplasia, severe intraventricular haemorrhage, white matter injury, neonatal early-onset sepsis, neonatal late-onset sepsis, necrotizing enterocolitis, or retinopathy of prematurity.

Secondary endpoints include pregnancy duration and maternal infectious morbidity. Additional secondary measures involve neonatal mild or moderate morbidity, specifically the prevalence of maternal or neonatal colonization or infection with ESBL-producing enterobacteria or third-generation cephalosporin-resistant enterobacteria. Furthermore, psychomotor development at 2 years of age will be evaluated using a parental auto-questionnaire.