N-acetylcysteine in Intra-amniotic Infection/Inflammation

Inflammation Clinical Trial

Official title:

Effect of N-acetylcysteine in Preventing Adverse Neonatal Outcomes in Women With Intra-amniotic Infection/Inflammation

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00397735
• Other study ID #: 0603001228
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: October 1, 2006
• Est. completion date: August 1, 2018

Study information

• Verified date: October 2018
• Source: Ohio State University
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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

Recruitment information / eligibility

• Status: Completed
• Enrollment: 68
• Est. completion date: August 1, 2018
• Est. primary completion date: October 29, 2012
• Accepts healthy volunteers: No
• Gender: Female
• Age group: 18 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Chorioamnionitis
• Communicable Diseases
• Fetal Membranes, Premature Rupture
• Infection
• Inflammation
• Labor, Premature
• Obstetric Labor, Premature
• Premature Birth
• Preterm Premature Rupture of the Membranes
• Rupture

Intervention

Procedure:
• amniocentesis
Amniotic fluid will be retrieved for routine amniocentesis to rule-out or confirm intra-amniotic infection and /or inflammation. The amniocentesis procedure will be clinically indicated and the patient will undergo the procedure independent of our study.

Drug:
• N-acetylcysteine or placebo
Only women with amniocentesis results consistent with infection/inflammation will be randomized

Locations

Country	Name	City	State
United States	The Research Institute at Nationwide Children's Hospital	Columbus	Ohio
United States	Yale New Haven Hospital	New Haven	Connecticut

Sponsors (1)

Lead Sponsor	Collaborator
Ohio State University

Country where clinical trial is conducted

United States, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	composite of mortality and severe short term neonatal morbidities (IVH, NEC, BPD, ROP, sepsis, newborn death)	IVH, NEC, BPD, ROP, Sepsis, death	up to 1 year
Secondary	neonatal sepsis	early and late neonatal sepsis	up to 30 days
Secondary	maternal and umbilical cord plasma antioxidant capacity	plasma antioxidant capacity	up to 1 day
Secondary	maternal and umbilical cord plasma N-acetylcysteine levels	N-acetylcysteine levels	up to 1 day
Secondary	umbilical cord levels of inflammatory cytokine concentrations	pannel of pro and anti inflammatory cytokines	up to 1 day
Secondary	funisitis grades	histology	up to 1 day
Secondary	maternal and umbilical cord blood glutathione concentration	glutathione levels	up to 1 day