- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT00397735
N-acetylcysteine in Intra-amniotic Infection/Inflammation
Effect of N-acetylcysteine in Preventing Adverse Neonatal Outcomes in Women With Intra-amniotic Infection/Inflammation
Study Overview
Status
Conditions
Intervention / Treatment
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
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
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Connecticut
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New Haven, Connecticut, United States, 06510
- Yale New Haven Hospital
-
-
Ohio
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Columbus, Ohio, United States, 43215
- The Research Institute at Nationwide Children's Hospital
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-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: Randomized
- Interventional Model: Parallel Assignment
- Masking: Quadruple
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: N-Acetylcysteine
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.
|
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.
Other Names:
Only women with amniocentesis results consistent with infection/inflammation will be randomized
Other Names:
|
Placebo Comparator: Placebo
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
|
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.
Other Names:
Only women with amniocentesis results consistent with infection/inflammation will be randomized
Other Names:
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
composite of mortality and severe short term neonatal morbidities (IVH, NEC, BPD, ROP, sepsis, newborn death)
Time Frame: up to 1 year
|
IVH, NEC, BPD, ROP, Sepsis, death
|
up to 1 year
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
neonatal sepsis
Time Frame: up to 30 days
|
early and late neonatal sepsis
|
up to 30 days
|
maternal and umbilical cord plasma antioxidant capacity
Time Frame: up to 1 day
|
plasma antioxidant capacity
|
up to 1 day
|
maternal and umbilical cord plasma N-acetylcysteine levels
Time Frame: up to 1 day
|
N-acetylcysteine levels
|
up to 1 day
|
umbilical cord levels of inflammatory cytokine concentrations
Time Frame: up to 1 day
|
pannel of pro and anti inflammatory cytokines
|
up to 1 day
|
funisitis grades
Time Frame: up to 1 day
|
histology
|
up to 1 day
|
maternal and umbilical cord blood glutathione concentration
Time Frame: up to 1 day
|
glutathione levels
|
up to 1 day
|
Collaborators and Investigators
Sponsor
Investigators
- Principal Investigator: Catalin S Buhimschi, MD, MBA, Ohio State University
Study record dates
Study Major Dates
Study Start
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Estimate)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Keywords
Additional Relevant MeSH Terms
- Pathologic Processes
- Wounds and Injuries
- Disease Attributes
- Fetal Diseases
- Pregnancy Complications
- Obstetric Labor Complications
- Placenta Diseases
- Inflammation
- Infections
- Communicable Diseases
- Chorioamnionitis
- Rupture
- Premature Birth
- Obstetric Labor, Premature
- Fetal Membranes, Premature Rupture
- Physiological Effects of Drugs
- Molecular Mechanisms of Pharmacological Action
- Anti-Infective Agents
- Antiviral Agents
- Protective Agents
- Respiratory System Agents
- Antioxidants
- Antidotes
- Free Radical Scavengers
- Expectorants
- Acetylcysteine
- N-monoacetylcystine
Other Study ID Numbers
- 0603001228
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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