Protective effect of azithromycin (AZM) to the pregnant women with preterm premature rupture of the membranes (pPROM) occurring at <28 weeks of gestation on the development of bronchopulmonary dysplasia in the neonates

JRCT ID: jRCTs031210631

Registered date:25/02/2022

Basic Information

• Recruitment status: Recruiting
• Health condition(s) or Problem(s) studied: preterm premature rupture of the membranes
• Date of first enrollment: 09/09/2022
• Target sample size: 100
• Study type: Interventional

Intervention(s)

Intervention group AZM administration
1) ABPC (Sulbacilin[R]) 1.5g intravenous drip (div). 4x/day 14 days (from Day1 to Day14).
2) AZM (Zithromax[R]) 500mg div. 1x/day 4 days (at Day1, Day2, Day 8, and Day 9).
3) AZM (Zithromax[R]) 250 mg orally 1x/day 10 days (from Day 3 to Day 7, and from Day 10 to Day 14).
Control group standard antibiotic administration
1) ABPC 1.5g div. 4x/day 14 days.
2) EM (Erythrocin[R]) 500mg div. 2x/day 4 days (at Day1, Day2, Day 8, and Day 9).
3) EM (Erythrocin[R]) 250mg tablets orally 4x/day 10 days (from Day 3 to Day 7, and from Day 10 to Day 14).

Outcome(s)

• Primary Outcome: Incidence rate of either moderate/severe BPD36 or intrauterine fetal death at or less than 36 weeks 0 days.

Secondary Outcome

(Efficacy evaluation items for mother)
Days from the onset of pPROM to the delivery, gestational weeks at delivery, Reasons of pregnancy termination, findings at delivery (mode of delivery, presence/absence of stillbirth, placental weight), incidence rate of intrauterine death [IUFD], incidence rate of histological chorioamnionitis [CAM], rate of cesarean delivery, incidence rate of placental abruption.
(Efficacy evaluation items for infant)
Incidence rate of BPD28, perinatal death rate (total of IUFD + early neonatal death [END] / total of neonatal live infants), rate of infantile death until just before discharge of the infants, birth weight, birth height, birth head circumference, day of hospitalization (from the birth date to the discharge), day of invasive ventilation, day of non-invasive ventilation, day of oxygen administration, incidence rate of infants with surfactant administration, incidence rate of infants with respiratory distress syndrome (RDS), incidence rate of infants with prolonged pulmonary hypertension, incidence rate of infants with intracranial hemorrhage (ICH), incidence rate of infants with periventricular leukomalacia (PVL), incidence rate of infants with sepsis, incidence rate of infants with necrotizing enterocolitis (NEC), incidence rate of infants with symptomatic patent ductus arteriosus (PDA).
(Safety evaluation items for mother and fetus)
Incidence rates of adverse events or side effects, incidence rates of severe adverse events or severe side effects, incidence rate of critical adverse events (fetal death, sepsis of mother, admission to intensive care unit (ICU) of mother, multiple organ disorders of mother, artificial ventilation for mother, hysterectomy for mother.
(Safety evaluation items for infants)
Incidence rates of severe adverse events.
(Other evaluation items in the current trial)
Detection rate of Ureaplasma species (at vagina, surface of placenta, infantile pharynx, and infantile ear cavity.

Key inclusion & exclusion criteria

• Age minimum: >= 18age old
• Age maximum: Not applicable
• Gender: Female

Include criteria

(1) Pregnant woman who gave consent on the participation for the current trial.
(2) Pregnant woman in whom the age at receiving informed consent is equal to or over than 18 years old.
(3) Pregnant woman with a singleton pregnancy who developed
preterm premature rupture of the membranes (pPROM) occurring at 22 weeks 0 days - 27 weeks 6 days.

Exclude criteria

(1) Pregnant woman with placenta previa.
(2) Pregnant woman with trachelectomy; However, pregnant woman with cervical incision should not be excluded, because such subject is at high risk for the occurrence of pPROM.
(3) Pregnant woman with hypertensive disorders of pregnancy (HDP); However, pregnant woman with chronic hypertension should not be excluded.
(4) Pregnant woman with a fetus who shows either AEDV or REDV before the onset of pPROM.
(5) Pregnant woman with any malignant tumors for whom the attending physicians consider the termination of pregnancy at very early pregnancy period.
(6) Pregnant woman with pPROM for whom the attending physicians consider the imminent termination of pregnancy at or soon after the onset of pPROM.
(7) Pregnant woman with pPROM who has had any diseases or symptoms by which the attending physicians consider the imminent termination of pregnancy at or soon after the onset of pPROM.
(8) Pregnant woman with the administration of AZM due to chlamydia infection within 2 weeks before the onset of pPROM.
(9) Pregnant woman with any kinds of antibiotics rather than either penicillin or cephem antibiotics for two weeks before the onset of pPROM.
(10) Pregnant woman who has been administered antibiotics rather than either ABPC or ABPC/SBT, from the onset of pPROM to the time obtaining consent; However, the following pregnant woman should not be excluded: when the administration of antibiotics rather than either ABPC or ABPC/SBT (excluding any kinds of macrolide antibiotics) were performed one day before the time of obtaining consent or earlier and the administration period of them were within 3 days.
(11) Pregnant woman with the administration of any kinds of macrolide antibiotics, from the onset of pPROM to the time obtaining consent.
(12) Pregnant woman with allergy for either penicillin or macrolide antibiotics.
(13) Pregnant woman complicated with infectious mononucleosis.
(14) Pregnant woman with a fetus with either chromosomal abnormalities or suspected severe multi-congenital anomaly syndrome.
(15) Pregnant woman with creatinine level of >=1.1 mg/dL at screening test just after obtaining consent.
(16) Pregnant woman complicated with QT syndrome.
(17) Pregnant woman with any types of psychological disorders for whom the attending physicians think that the patients should not be participated in the current trial.
(18) Pregnant woman for whom the attending physicians think that the patients should not be participated in the current trial, because there are some reasons which will disturb the achievement of the trial.

Related Information

• Primary Sponsor: Ohkuchi Akihide
• Source(s) of Monetary Support: Japan Agency for Medical Research and Development