Clinical trial NCT00397735: N-acetylcysteine in Intra-amniotic Infection/Inflammation
Official title: Effect of N-acetylcysteine in Preventing Adverse Neonatal Outcomes in Women With Intra-amniotic Infection/Inflammation
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Labor, Premature
Preterm Premature Rupture of the Membranes
Infection
Inflammation
Chorioamnionitis
Keywords: pregnancy
chorioamnionitis
preterm labor
preterm premature rupture of the membranes
Intra-amniotic infection
Intra-amniotic inflammation
Lead sponsor: Ohio State University
Sponsor class: OTHER
First posted: 2006-11-09
Enrollment: 68
Sex: FEMALE
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: The aim of the study is to determine if N-acetylcysteine (a potent free radical scavenger) prevents the occurrence of adverse neonatal outcomes in preterm deliveries complicated by infection associated with preterm labor or preterm premature rupture of membranes (PPROM). The working hypothesis is that in pregnancies complicated by intra-amniotic infection or inflammation, N-acetylcysteine protects the fetus by preventing the development, or decreasing the intensity and/or progression of the fetal inflammatory syndrome.

Detailed description: Despite extensive research, the etiology of most preterm births remains unknown. There are significant fetal consequences associated with preterm birth, which include necrotizing enterocolitis, fetal respiratory distress and intra-ventricular hemorrhage. Perinatal mortality is about 44%, 11% and 5% when deliveries occur between 25-28 weeks, 29-32 weeks and 33-34 weeks, respectively. While for many years, it was assumed that the cause of the high morbidity associated with prematurity was the birth of a neonate with a restricted adaptive capacity, it has also been suggested that part of the high perinatal morbidity was the consequence of adverse processes affecting the fetus in utero, rather than of prematurity per se. Intra-amniotic inflammation present in utero early in gestation may trigger the cascade of events leading to preterm birth (i.e. rupture of membranes, cervical ripening, uterine contractions) and provide an intrauterine milieu which is unfavorable or even harmful to the fetus.

Most living organisms have developed well-integrated, antioxidant defenses to scavenge free radicals and control their intracellular concentration. A loss of balance between free radicals and antioxidants (the redox balance) is one mechanism of cell injury in diseases associated with inflammation. N-acetylcysteine is an approved anti-oxidant medication drug used during pregnancy for treatment of mothers with acetaminophen (Tylenol) toxicity. N-acetylcysteine has been safely administered during pregnancy in over 100 women who overdosed with Tylenol and to preterm and healthy term newborns for other purposes. It is a goal of our trial to prevent free radical formation by administering N-acetylcysteine and to further study whether the outcome of preterm deliveries will improve compared to a control group which will not receive placebo infusion

Eligibility criteria: Inclusion Criteria:

* Women admitted onto the Labor and Birth Ward or Maternal Special Care Units of the Yale New Haven Hospital who have a clinically indicated amniocentesis which demonstrates presence of intra-amniotic infection and/or inflammation.

Exclusion Criteria:

* Patients that require immediate intervention or close medical supervision (cardiac and renal disease, congestive heart failure, history of asthma), maternal infection (HIV, hepatitis B or C), cord prolapse, known fetal malformation, allergic reactions to N-acetylcysteine, preeclampsia

Primary outcomes:
measure: composite of mortality and severe short term neonatal morbidities (IVH, NEC, BPD, ROP, sepsis, newborn death)
timeFrame: up to 1 year
Secondary outcomes:
measure: neonatal sepsis
timeFrame: up to 30 days
measure: maternal and umbilical cord plasma antioxidant capacity
timeFrame: up to 1 day
measure: maternal and umbilical cord plasma N-acetylcysteine levels
timeFrame: up to 1 day
measure: umbilical cord levels of inflammatory cytokine concentrations
timeFrame: up to 1 day
measure: funisitis grades
timeFrame: up to 1 day
measure: maternal and umbilical cord blood glutathione concentration
timeFrame: up to 1 day
Other outcomes:
Locations:
city: New Haven
country: United States
facility: Yale New Haven Hospital
state: Connecticut
city: Columbus
country: United States
facility: The Research Institute at Nationwide Children's Hospital
state: Ohio
Study officials:
affiliation: Ohio State University
name: Catalin S Buhimschi, MD, MBA
role: PRINCIPAL_INVESTIGATOR
References: