Working...
ClinicalTrials.gov
ClinicalTrials.gov Menu

Safety of N-acetylcysteine in Maternal Chorioamnionitis (NAC in Chorio)

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT00724594
Recruitment Status : Completed
First Posted : July 29, 2008
Results First Posted : April 30, 2015
Last Update Posted : November 27, 2018
Sponsor:
Collaborator:
National Institute of Neurological Disorders and Stroke (NINDS)
Information provided by (Responsible Party):
Dorothea D. Jenkins, Medical University of South Carolina

Study Type Interventional
Study Design Allocation: Randomized;   Intervention Model: Parallel Assignment;   Masking: Single (Participant);   Primary Purpose: Treatment
Conditions Chorioamnionitis
Brain Injury
Interventions Drug: N-acetylcysteine
Drug: Control
Enrollment 46
Recruitment Details  
Pre-assignment Details Due two enrolling two sets of twins (one set in the preterm/NAC group, and one set in the preterm/control group), our study included 24 infants and 22 mothers.
Arm/Group Title NAC Infant Control Infant NAC Maternal Control Maternal
Hide Arm/Group Description Infants treated with N-acetylcysteine Infants treated with saline Mothers of infants treated with N-acetylcysteine Mothers of infants treated with saline
Period Title: Overall Study
Started 12 12 11 11
Completed 12 12 11 10
Not Completed 0 0 0 1
Arm/Group Title NAC Infant Control Infant NAC Maternal Control Maternal Total
Hide Arm/Group Description Infants treated with N-acetylcysteine Infants treated with saline Mothers of infants treated with N-acetylcysteine Mothers of infants treated with saline Total of all reporting groups
Overall Number of Baseline Participants 12 12 11 11 46
Hide Baseline Analysis Population Description
[Not Specified]
Age, Customized  
Measure Type: Number
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 11 participants 11 participants 46 participants
Preterm Infants 7 7 NA [1]  NA [1]  NA [2] 
Term Infants 5 5 NA [1]  NA [1]  NA [2] 
Mothers aged 18-45years NA [3]  NA [3]  11 11 NA [2] 
[1]
Only applicable to infants
[2]
Total not calculated because data are not available (NA) in one or more arms.
[3]
Only applicable to mothers
Sex: Female, Male  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 11 participants 11 participants 46 participants
Female
5
  41.7%
6
  50.0%
11
 100.0%
11
 100.0%
33
  71.7%
Male
7
  58.3%
6
  50.0%
0
   0.0%
0
   0.0%
13
  28.3%
Race (NIH/OMB)  
Measure Type: Count of Participants
Unit of measure:  Participants
Number Analyzed 12 participants 12 participants 11 participants 11 participants 46 participants
American Indian or Alaska Native
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Asian
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Native Hawaiian or Other Pacific Islander
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Black or African American
9
  75.0%
5
  41.7%
8
  72.7%
4
  36.4%
26
  56.5%
White
3
  25.0%
7
  58.3%
3
  27.3%
7
  63.6%
20
  43.5%
More than one race
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Unknown or Not Reported
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
0
   0.0%
Region of Enrollment  
Measure Type: Number
Unit of measure:  Participants
United States Number Analyzed 12 participants 12 participants 11 participants 11 participants 46 participants
12 12 11 11 46
1.Primary Outcome
Title NAC Terminal Elimination Half-life
Hide Description [Not Specified]
Time Frame prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title NAC Maternal NAC Preterm Infants NAC Term Infants
Hide Arm/Group Description:
Mothers treated with N-acetylcysteine prior to delivery of infant
Preterm infants treated with N-acetylcysteine
Term infants treated with N-acetylcysteine
Overall Number of Participants Analyzed 11 7 5
Mean (Standard Deviation)
Unit of Measure: hours
1.2  (0.2) 7.5  (2.0) 5.1  (1.3)
2.Primary Outcome
Title NAC Volume of Distribution
Hide Description [Not Specified]
Time Frame prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title NAC Maternal NAC Preterm Infants NAC Term Infants
Hide Arm/Group Description:
Mothers treated with N-acetylcysteine prior to delivery of infant
Preterm infants treated with N-acetylcysteine
Term infants treated with N-acetylcysteine
Overall Number of Participants Analyzed 11 7 5
Mean (Standard Deviation)
Unit of Measure: L/kg
0.41  (0.07) 0.47  (0.04) 0.38  (0.09)
3.Primary Outcome
Title NAC Total Body Clearance
Hide Description [Not Specified]
Time Frame prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title NAC Maternal NAC Preterm Infants NAC Term Infants
Hide Arm/Group Description:
Mothers treated with N-acetylcysteine prior to delivery of infant
Preterm infants treated with N-acetylcysteine
Term infants treated with N-acetylcysteine
Overall Number of Participants Analyzed 11 7 5
Mean (Standard Deviation)
Unit of Measure: mL/h/kg
255  (61) 45.0  (8.2) 53.7  (11.3)
4.Primary Outcome
Title NAC Concentrations
Hide Description [Not Specified]
Time Frame Peak: 30 minutes after NAC infusion. Cord: at delivery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title NAC Maternal NAC Preterm Infants NAC Term Infants
Hide Arm/Group Description:
Mothers treated with N-acetylcysteine prior to delivery
Preterm infants treated with N-acetylcysteine
Term infants treated with N-acetylcysteine
Overall Number of Participants Analyzed 11 7 5
Mean (Standard Deviation)
Unit of Measure: micromol/L
Peak NAC concentration in plasma 1222  (415) 49.0  (14.9) 92.3  (69.2)
NAC cord concentration NA [1]   (NA) 370.7  (199.2) 639.7  (409.4)
[1]
Not applicable to mothers
5.Primary Outcome
Title Placental Transfer Ratio
Hide Description Ratio of NAC concentration in cord to maternal venous blood
Time Frame At time of delivery
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title NAC Maternal
Hide Arm/Group Description:
Mothers treated with N-acetylcysteine prior to birth
Overall Number of Participants Analyzed 12
Mean (Standard Deviation)
Unit of Measure: ratio
1.4  (0.8)
6.Primary Outcome
Title Maternal and Infant Mean Blood Pressure Change
Hide Description [Not Specified]
Time Frame Maternal mean BP changes were pre/post dosing prior to delivery. Infant measurements were pre/post their first dosing
Hide Outcome Measure Data
Hide Analysis Population Description
The infant and maternal populations analyzed for this portion are incomplete, as not all individuals had paired before/after blood pressure measurements at this time point.
Arm/Group Title NAC Infants Control Infants NAC Maternal Control Maternal
Hide Arm/Group Description:
Infants treated with N-acetylcysteine
Infants treated with saline
Mothers treated with N-acetylcysteine prior to delivery
Mothers treated with saline prior to delivery
Overall Number of Participants Analyzed 10 7 11 10
Mean (Standard Deviation)
Unit of Measure: mmHg
-1.2  (13) 2.1  (11) 1  (12) 2  (10)
7.Primary Outcome
Title Cerebral Blood Flow
Hide Description Resistive index in middle cerebral artery (MCA)
Time Frame after NAC infusion
Hide Outcome Measure Data
Hide Analysis Population Description
blood flow resistive indices after first dose of N-acetylcysteine or saline
Arm/Group Title NAC Term Infants Control Term Infants NAC Preterm Infants Control Preterm Infants
Hide Arm/Group Description:
Term Infants treated with N-acetylcysteine
Term Infants treated with saline
Preterm Infants treated with N-acetylcysteine
Preterm Infants treated with saline
Overall Number of Participants Analyzed 5 4 6 5
Mean (95% Confidence Interval)
Unit of Measure: ratio
0.93
(0.87 to 0.99)
0.89
(0.81 to 0.97)
0.92
(0.88 to 0.97)
0.89
(0.82 to 0.95)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NAC Term Infants, Control Term Infants
Comments Term infant cohort : NAC vs control H0= there will be no difference in resistive index in Middle Cerebral Artery after N-acetylcysteine or saline in the term cohort.
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9
Comments not significant
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection NAC Preterm Infants, Control Preterm Infants
Comments Preterm infant cohort: NAC vs control H0= there will be no difference in resisitive index in MCA after N-acetylcysteine or saline in preterm cohort
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
8.Primary Outcome
Title Prothrombin Time
Hide Description prothrombin clotting time
Time Frame after N-acetylcystiene or saline infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title NAC Infant Control Infant NAC Maternal Control Maternal
Hide Arm/Group Description:
Infants treated with N-acetylcysteine
Infants treated with saline
Mothers of infants treated with N-acetylcysteine
Mothers of infants treated with saline
Overall Number of Participants Analyzed 8 6 11 11
Mean (Standard Deviation)
Unit of Measure: seconds
19.5  (2.5) 19.0  (4.0) 14.2  (0.6) 14.4  (1.2)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NAC Maternal, Control Maternal
Comments Maternal cohort: NAC versus control l H0= PT will not be different in mothers after NAC or saline
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9
Comments not significant
Method t-test, 2 sided
Comments [Not Specified]
Show Statistical Analysis 2 Hide Statistical Analysis 2
Statistical Analysis Overview Comparison Group Selection NAC Infant, Control Infant
Comments Infant cohort: NAC versus control H0= prothrombin time will not be different in the infants after NAC or saline
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.9
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
9.Secondary Outcome
Title Magnetic Resonance Spectroscopy of Infants
Hide Description [Not Specified]
Time Frame 36 - 40 weeks gestational age
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title NAC Infants Control Infants
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 7 9
Mean (Standard Deviation)
Unit of Measure: ratio of myoInositol/NAA in basal gangli
1.09  (0.31) 1.34  (0.20)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NAC Infants, Control Infants
Comments correcting for gestational age at birth
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.072
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
10.Secondary Outcome
Title Cytokine Level IL-1Ra in Plasma
Hide Description anti-inflammatory cytokine Interleukin -1 Receptor alpha (IL-1Ra)
Time Frame after N-acetylcysteine infusion
Hide Outcome Measure Data
Hide Analysis Population Description
[Not Specified]
Arm/Group Title NAC Infants Control Infants
Hide Arm/Group Description:
[Not Specified]
[Not Specified]
Overall Number of Participants Analyzed 12 9
Median (Inter-Quartile Range)
Unit of Measure: IL-1Ra pg/ml
745
(251 to 1302)
8.3
(8.3 to 448)
Show Statistical Analysis 1 Hide Statistical Analysis 1
Statistical Analysis Overview Comparison Group Selection NAC Infants, Control Infants
Comments [Not Specified]
Type of Statistical Test Other
Comments [Not Specified]
Statistical Test of Hypothesis P-Value 0.014
Comments [Not Specified]
Method t-test, 2 sided
Comments [Not Specified]
Time Frame Mothers were monitored for Adverse Events for up to 2 days after treatment. Infants were assessed for Adverse Events until discharge, Serious Adverse Events up to 30 days post-treatment.
Adverse Event Reporting Description [Not Specified]
 
Arm/Group Title NAC Infant Control Infant NAC Maternal Control Maternal
Hide Arm/Group Description Infants treated with N-acetylcysteine Infants treated with saline Mothers of infants treated with N-acetylcysteine Mothers of infants treated with saline
All-Cause Mortality
NAC Infant Control Infant NAC Maternal Control Maternal
Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%) Affected / at Risk (%)
Total   --/--      --/--      --/--      --/--    
Show Serious Adverse Events Hide Serious Adverse Events
NAC Infant Control Infant NAC Maternal Control Maternal
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   4/12 (33.33%)      3/12 (25.00%)      0/11 (0.00%)      0/11 (0.00%)    
General disorders         
Death  [1]  0/12 (0.00%)  0 1/12 (8.33%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Immune system disorders         
Pneumonia   1/12 (8.33%)  1 0/12 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Culture Proven Sepsis   1/12 (8.33%)  1 1/12 (8.33%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Nervous system disorders         
IVH 1-2 days of age   1/12 (8.33%)  1 1/12 (8.33%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
IVH 5-7 days of age   2/12 (16.67%)  2 0/12 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
NEC within 30 days   1/12 (8.33%)  1 1/12 (8.33%)  1 0/11 (0.00%)  0 0/11 (0.00%)  0
Hypoxic Ischemic Encephalopathy   1/12 (8.33%)  1 0/12 (0.00%)  0 0/11 (0.00%)  0 0/11 (0.00%)  0
Indicates events were collected by systematic assessment
[1]
Resuscitation-chest compressions/CV meds
Show Other (Not Including Serious) Adverse Events Hide Other (Not Including Serious) Adverse Events
Frequency Threshold for Reporting Other Adverse Events 0%
NAC Infant Control Infant NAC Maternal Control Maternal
Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events Affected / at Risk (%) # Events
Total   5/12 (41.67%)      3/12 (25.00%)      2/11 (18.18%)      2/11 (18.18%)    
Blood and lymphatic system disorders         
Hypotension   0/12 (0.00%)  0 1/12 (8.33%)  1 1/11 (9.09%)  1 1/11 (9.09%)  1
Prolonged PT time   5/8 (62.50%)  5 3/6 (50.00%)  3 0/11 (0.00%)  0 0/11 (0.00%)  0
Respiratory, thoracic and mediastinal disorders         
Shortness of breath/wheezing   0/12 (0.00%)  0 0/12 (0.00%)  0 0/11 (0.00%)  0 1/11 (9.09%)  1
Skin and subcutaneous tissue disorders         
Rash/Hives   0/12 (0.00%)  0 0/12 (0.00%)  0 1/11 (9.09%)  1 0/11 (0.00%)  0
Indicates events were collected by systematic assessment
Certain Agreements
Principal Investigators are NOT employed by the organization sponsoring the study.
There is NOT an agreement between Principal Investigators and the Sponsor (or its agents) that restricts the PI's rights to discuss or publish trial results after the trial is completed.
Results Point of Contact
Name/Title: Dr. Dorothea Jenkins
Organization: Medical University of South Carolina
Phone: 843-792-4341
Responsible Party: Dorothea D. Jenkins, Medical University of South Carolina
ClinicalTrials.gov Identifier: NCT00724594     History of Changes
Other Study ID Numbers: R01NS052448 ( U.S. NIH Grant/Contract )
R01NS052448 ( U.S. NIH Grant/Contract )
First Submitted: July 28, 2008
First Posted: July 29, 2008
Results First Submitted: January 9, 2015
Results First Posted: April 30, 2015
Last Update Posted: November 27, 2018