N-acetylcysteine in Intra-amniotic Infection/Inflammation

NCT00397735 | Completed Phase 1

• 1 other identifier: 0603001228
• Study Type: interventional
• Target: 68
• Locations: 1 country
• Sites: 2

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.

Conditions

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

Outcome Measures

Primary Outcomes (1)

• 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 Outcomes (6)

• neonatal sepsis

  up to 30 days

• maternal and umbilical cord plasma antioxidant capacity

  up to 1 day

• maternal and umbilical cord plasma N-acetylcysteine levels

  up to 1 day

• umbilical cord levels of inflammatory cytokine concentrations

  up to 1 day

• funisitis grades

  up to 1 day

Study Arms (2)

N-Acetylcysteine

EXPERIMENTAL

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; Drug: N-acetylcysteine or placebo

Placebo

PLACEBO COMPARATOR

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; Drug: N-acetylcysteine or placebo

Interventions

amniocentesis PROCEDURE

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.

Also known as: transabdominal amniocentesis

N-Acetylcysteine; Placebo

N-acetylcysteine or placebo DRUG

Only women with amniocentesis results consistent with infection/inflammation will be randomized

Also known as: Mucomyst, Acetadote

N-Acetylcysteine; Placebo

Eligibility Criteria

• Age: 18 Years+
• Sex: female
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• Ohio State University: lead

Study Sites (2)

Yale New Haven Hospital

New Haven, Connecticut, 06510, United States

Location

The Research Institute at Nationwide Children's Hospital

Columbus, Ohio, 43215, United States

Location

MeSH Terms

Conditions

Obstetric Labor, Premature; Preterm Premature Rupture of the Membranes; Infections; Inflammation; Chorioamnionitis

Interventions

Amniocentesis; Acetylcysteine

Condition Hierarchy (Ancestors)

Obstetric Labor Complications; Pregnancy Complications; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms; Fetal Diseases; Fetal Membranes, Premature Rupture; Placenta Diseases; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Cytodiagnosis; Cytological Techniques; Clinical Laboratory Techniques; Diagnostic Techniques and Procedures; Diagnosis; Paracentesis; Specimen Handling; Prenatal Diagnosis; Diagnostic Techniques, Obstetrical and Gynecological; Punctures; Surgical Procedures, Operative; Investigative Techniques; Cysteine; Amino Acids, Sulfur; Sulfur Compounds; Organic Chemicals; Amino Acids; Amino Acids, Peptides, and Proteins

Study Officials

• Catalin S Buhimschi, MD, MBA

  Ohio State University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Obsterics and Gynecology; Frederick Zuspan Endowed Chair

Study Record Dates

• First Submitted: November 7, 2006
• First Posted: November 9, 2006
• Study Start: October 1, 2006
• Primary Completion: October 29, 2012
• Study Completion: August 1, 2018
• Last Updated: October 10, 2018

Record last verified: 2018-10

Locations

US (2)