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N-acetylcysteine in Intra-amniotic Infection/Inflammation

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ClinicalTrials.gov Identifier: NCT00397735
Recruitment Status : Completed
First Posted : November 9, 2006
Last Update Posted : October 10, 2018
Sponsor:
Information provided by (Responsible Party):
Catalin S Buhimschi, MD, Ohio State University

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.

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

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 : Interventional  (Clinical Trial)
Actual Enrollment : 68 participants
Allocation: Randomized
Intervention Model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary Purpose: Treatment
Official Title: Effect of N-acetylcysteine in Preventing Adverse Neonatal Outcomes in Women With Intra-amniotic Infection/Inflammation
Study Start Date : October 1, 2006
Actual Primary Completion Date : October 29, 2012
Actual Study Completion Date : August 1, 2018

Resource links provided by the National Library of Medicine


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.
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




Primary Outcome Measures :
  1. 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


Secondary Outcome Measures :
  1. neonatal sepsis [ Time Frame: up to 30 days ]
    early and late neonatal sepsis

  2. maternal and umbilical cord plasma antioxidant capacity [ Time Frame: up to 1 day ]
    plasma antioxidant capacity

  3. maternal and umbilical cord plasma N-acetylcysteine levels [ Time Frame: up to 1 day ]
    N-acetylcysteine levels

  4. umbilical cord levels of inflammatory cytokine concentrations [ Time Frame: up to 1 day ]
    pannel of pro and anti inflammatory cytokines

  5. funisitis grades [ Time Frame: up to 1 day ]
    histology

  6. maternal and umbilical cord blood glutathione concentration [ Time Frame: up to 1 day ]
    glutathione levels



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Ages Eligible for Study:   18 Years and older   (Adult, Older Adult)
Sexes 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

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT00397735


Locations
United States, Connecticut
Yale New Haven Hospital
New Haven, Connecticut, United States, 06510
United States, Ohio
The Research Institute at Nationwide Children's Hospital
Columbus, Ohio, United States, 43215
Sponsors and Collaborators
Ohio State University
Investigators
Principal Investigator: Catalin S Buhimschi, MD, MBA Ohio State University

Responsible Party: Catalin S Buhimschi, MD, Professor of Obsterics and Gynecology; Frederick Zuspan Endowed Chair, Ohio State University
ClinicalTrials.gov Identifier: NCT00397735     History of Changes
Other Study ID Numbers: 0603001228
First Posted: November 9, 2006    Key Record Dates
Last Update Posted: October 10, 2018
Last Verified: October 2018

Keywords provided by Catalin S Buhimschi, MD, Ohio State University:
pregnancy
chorioamnionitis
preterm labor
preterm premature rupture of the membranes
Intra-amniotic infection
Intra-amniotic inflammation

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