N-acetylcysteine in Intra-amniotic Infection/Inflammation

This study is currently recruiting participants. (see Contacts and Locations)
Verified July 2012 by Yale University
Sponsor:
Information provided by (Responsible Party):
Catalin Buhimschi, Yale University
ClinicalTrials.gov Identifier:
NCT00397735
First received: November 7, 2006
Last updated: July 18, 2012
Last verified: July 2012
  Purpose

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.


Condition Intervention Phase
Labor, Premature
Preterm Premature Rupture of the Membranes
Infection
Inflammation
Chorioamnionitis
Procedure: amniocentesis
Drug: N-acetylcysteine or placebo
Phase 1
Phase 2

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Caregiver, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of N-acetylcysteine in Preventing Adverse Neonatal Outcomes in Women With Intra-amniotic Infection/Inflammation

Resource links provided by NLM:


Further study details as provided by Yale University:

Primary Outcome Measures:
  • early onset neonatal sepsis [ Time Frame: within 3 days of postnatal life ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • maternal and umbilical cord plasma N-acetylcysteine levels [ Time Frame: within peripartum period ] [ Designated as safety issue: No ]
  • maternal and umbilical cord plasma antioxidant capacity [ Time Frame: within peripartum period ] [ Designated as safety issue: No ]
  • maternal and umbilical cord blood glutathione concentration [ Time Frame: within peripartum period ] [ Designated as safety issue: No ]
  • umbilical cord levels of inflammatory cytokine concentrations [ Time Frame: at birth ] [ Designated as safety issue: No ]
  • funisitis grades [ Time Frame: at birth ] [ Designated as safety issue: No ]
  • other neonatal outcomes (respiratory distress syndrome, necrotizing enterocolitis, intraventricular hemorrhage, retinopathy of prematurity, late-onset sepsis, bronchopulmonary dysplasia) [ Time Frame: within the period of admission in neonatal intensive care ] [ Designated as safety issue: No ]

Estimated Enrollment: 140
Study Start Date: October 2006
Estimated Study Completion Date: April 2015
Estimated Primary Completion Date: November 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
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.
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.
Other Name: transabdominal amniocentesis
Drug: N-acetylcysteine or placebo
Only women with amniocentesis results consistent with infection/inflammation will be randomized
Other Names:
  • Mucomyst
  • Acetadote
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
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.
Other Name: transabdominal amniocentesis
Drug: N-acetylcysteine or placebo
Only women with amniocentesis results consistent with infection/inflammation will be randomized
Other Names:
  • Mucomyst
  • Acetadote

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Female
Accepts Healthy Volunteers:   No
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
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT00397735

Contacts
Contact: Catalin S Buhimschi, MD 203-785-4536 catalin.buhimschi@yale.edu
Contact: Irina A Buhimschi, MD 203-785-6164 irina.buhimschi@yale.edu

Locations
United States, Connecticut
Yale New Haven Hospital Recruiting
New Haven, Connecticut, United States, 06510
Sponsors and Collaborators
Yale University
Investigators
Principal Investigator: Catalin S Buhimschi, MD Yale University
  More Information

Additional Information:
No publications provided

Responsible Party: Catalin Buhimschi, Associate Professor, Director Perinatal Reserach, Yale University
ClinicalTrials.gov Identifier: NCT00397735     History of Changes
Other Study ID Numbers: 0603001228
Study First Received: November 7, 2006
Last Updated: July 18, 2012
Health Authority: United States: Institutional Review Board

Keywords provided by Yale University:
pregnancy
chorioamnionitis
preterm labor
preterm premature rupture of the membranes
Intra-amniotic infection
Intra-amniotic inflammation

Additional relevant MeSH terms:
Fetal Diseases
Chorioamnionitis
Inflammation
Obstetric Labor, Premature
Fetal Membranes, Premature Rupture
Rupture
Pregnancy Complications
Obstetric Labor Complications
Placenta Diseases
Pathologic Processes
Wounds and Injuries
Acetylcysteine
N-monoacetylcystine
Antiviral Agents
Anti-Infective Agents
Therapeutic Uses
Pharmacologic Actions
Expectorants
Respiratory System Agents
Free Radical Scavengers
Antioxidants
Molecular Mechanisms of Pharmacological Action
Protective Agents
Physiological Effects of Drugs
Antidotes

ClinicalTrials.gov processed this record on September 11, 2014