search
Back to results

N-acetylcysteine in Intra-amniotic Infection/Inflammation

Primary Purpose

Labor, Premature, Preterm Premature Rupture of the Membranes, Infection

Status
Completed
Phase
Phase 1
Locations
United States
Study Type
Interventional
Intervention
amniocentesis
N-acetylcysteine or placebo
Sponsored by
Ohio State University
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Labor, Premature focused on measuring pregnancy, chorioamnionitis, preterm labor, preterm premature rupture of the membranes, Intra-amniotic infection, Intra-amniotic inflammation

Eligibility Criteria

18 Years - undefined (Adult, Older Adult)FemaleDoes not accept healthy volunteers

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

Sites / Locations

  • Yale New Haven Hospital
  • The Research Institute at Nationwide Children's Hospital

Arms of the Study

Arm 1

Arm 2

Arm Type

Experimental

Placebo Comparator

Arm Label

N-Acetylcysteine

Placebo

Arm Description

The subjects enrolled in our research protocol must have evidence of infection/inflammation at amniocentesis in order to receive N-acetylcysteine. Women with positive amniocentesis results The dose of N-acetylcysteine is the one recommended to be used in humans to prevent acetaminophen toxicity: 150 mg/kg loading dose (60 min), followed by 50mg/kg IV continuous infusion rate for 4 hours, and followed by 100 mg/kg IV continuous infusion rate for the following 16 hours. Acetadote (Cumberland Pharmaceuticals) is the only FDA-approved intravenous N-acetylcysteine formulation and will be used in our study.

The subjects enrolled in our research protocol must have infection/inflammation in order to be randomized to receive N-acetylcysteine or placebo. Placebo-assigned patients will receive sodium chloride solution without N-acetylcysteine

Outcomes

Primary Outcome Measures

composite of mortality and severe short term neonatal morbidities (IVH, NEC, BPD, ROP, sepsis, newborn death)
IVH, NEC, BPD, ROP, Sepsis, death

Secondary Outcome Measures

neonatal sepsis
early and late neonatal sepsis
maternal and umbilical cord plasma antioxidant capacity
plasma antioxidant capacity
maternal and umbilical cord plasma N-acetylcysteine levels
N-acetylcysteine levels
umbilical cord levels of inflammatory cytokine concentrations
pannel of pro and anti inflammatory cytokines
funisitis grades
histology
maternal and umbilical cord blood glutathione concentration
glutathione levels

Full Information

First Posted
November 7, 2006
Last Updated
October 8, 2018
Sponsor
Ohio State University
search

1. Study Identification

Unique Protocol Identification Number
NCT00397735
Brief Title
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

2. Study Status

Record Verification Date
October 2018
Overall Recruitment Status
Completed
Study Start Date
October 1, 2006 (undefined)
Primary Completion Date
October 29, 2012 (Actual)
Study Completion Date
August 1, 2018 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Principal Investigator
Name of the Sponsor
Ohio State University

4. Oversight

Data Monitoring Committee
No

5. Study Description

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

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
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

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Parallel Assignment
Masking
ParticipantCare ProviderInvestigatorOutcomes Assessor
Allocation
Randomized
Enrollment
68 (Actual)

8. Arms, Groups, and Interventions

Arm Title
N-Acetylcysteine
Arm Type
Experimental
Arm Description
The subjects enrolled in our research protocol must have evidence of infection/inflammation at amniocentesis in order to receive N-acetylcysteine. Women with positive amniocentesis results The dose of N-acetylcysteine is the one recommended to be used in humans to prevent acetaminophen toxicity: 150 mg/kg loading dose (60 min), followed by 50mg/kg IV continuous infusion rate for 4 hours, and followed by 100 mg/kg IV continuous infusion rate for the following 16 hours. Acetadote (Cumberland Pharmaceuticals) is the only FDA-approved intravenous N-acetylcysteine formulation and will be used in our study.
Arm Title
Placebo
Arm Type
Placebo Comparator
Arm Description
The subjects enrolled in our research protocol must have infection/inflammation in order to be randomized to receive N-acetylcysteine or placebo. Placebo-assigned patients will receive sodium chloride solution without N-acetylcysteine
Intervention Type
Procedure
Intervention Name(s)
amniocentesis
Other Intervention Name(s)
transabdominal amniocentesis
Intervention Description
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.
Intervention Type
Drug
Intervention Name(s)
N-acetylcysteine or placebo
Other Intervention Name(s)
Mucomyst, Acetadote
Intervention Description
Only women with amniocentesis results consistent with infection/inflammation will be randomized
Primary Outcome Measure Information:
Title
composite of mortality and severe short term neonatal morbidities (IVH, NEC, BPD, ROP, sepsis, newborn death)
Description
IVH, NEC, BPD, ROP, Sepsis, death
Time Frame
up to 1 year
Secondary Outcome Measure Information:
Title
neonatal sepsis
Description
early and late neonatal sepsis
Time Frame
up to 30 days
Title
maternal and umbilical cord plasma antioxidant capacity
Description
plasma antioxidant capacity
Time Frame
up to 1 day
Title
maternal and umbilical cord plasma N-acetylcysteine levels
Description
N-acetylcysteine levels
Time Frame
up to 1 day
Title
umbilical cord levels of inflammatory cytokine concentrations
Description
pannel of pro and anti inflammatory cytokines
Time Frame
up to 1 day
Title
funisitis grades
Description
histology
Time Frame
up to 1 day
Title
maternal and umbilical cord blood glutathione concentration
Description
glutathione levels
Time Frame
up to 1 day

10. Eligibility

Sex
Female
Minimum Age & Unit of Time
18 Years
Accepts Healthy Volunteers
No
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
Overall Study Officials:
First Name & Middle Initial & Last Name & Degree
Catalin S Buhimschi, MD, MBA
Organizational Affiliation
Ohio State University
Official's Role
Principal Investigator
Facility Information:
Facility Name
Yale New Haven Hospital
City
New Haven
State/Province
Connecticut
ZIP/Postal Code
06510
Country
United States
Facility Name
The Research Institute at Nationwide Children's Hospital
City
Columbus
State/Province
Ohio
ZIP/Postal Code
43215
Country
United States

12. IPD Sharing Statement

Learn more about this trial

N-acetylcysteine in Intra-amniotic Infection/Inflammation

We'll reach out to this number within 24 hrs