Trial Outcomes & Findings for Safety of N-acetylcysteine in Maternal Chorioamnionitis (NAC in Chorio) (NCT NCT00724594)

NCT ID: NCT00724594

Last Updated: 2021-04-12

Results Overview

• Recruitment status: COMPLETED
• Study phase: PHASE1/PHASE2
• Target enrollment: 46 participants
• Primary outcome timeframe: prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion
• Results posted on: 2021-04-12

Participant Flow

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.

Participant milestones

Measure	NAC Infant Infants treated with N-acetylcysteine	Control Infant Infants treated with saline	NAC Maternal Mothers of infants treated with N-acetylcysteine	Control Maternal Mothers of infants treated with saline
Overall Study STARTED	12	12	11	11
Overall Study COMPLETED	12	12	11	10
Overall Study NOT COMPLETED	0	0	0	1

Reasons for withdrawal

Withdrawal data not reported

Baseline Characteristics

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

Baseline characteristics by cohort

Measure	NAC Infant n=12 Participants Infants treated with N-acetylcysteine	Control Infant n=12 Participants Infants treated with saline	NAC Maternal n=11 Participants Mothers of infants treated with N-acetylcysteine	Control Maternal n=11 Participants Mothers of infants treated with saline	Total n=46 Participants Total of all reporting groups
Age, Customized Preterm Infants	7 participants n=5 Participants	7 participants n=7 Participants	NA participants n=5 Participants	NA participants n=4 Participants	NA participants n=21 Participants
Age, Customized Term Infants	5 participants n=5 Participants	5 participants n=7 Participants	NA participants n=5 Participants	NA participants n=4 Participants	NA participants n=21 Participants
Age, Customized Mothers aged 18-45years	NA participants n=5 Participants	NA participants n=7 Participants	11 participants n=5 Participants	11 participants n=4 Participants	NA participants n=21 Participants
Sex: Female, Male Female	5 Participants n=5 Participants	6 Participants n=7 Participants	11 Participants n=5 Participants	11 Participants n=4 Participants	33 Participants n=21 Participants
Sex: Female, Male Male	7 Participants n=5 Participants	6 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	13 Participants n=21 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Asian	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Black or African American	9 Participants n=5 Participants	5 Participants n=7 Participants	8 Participants n=5 Participants	4 Participants n=4 Participants	26 Participants n=21 Participants
Race (NIH/OMB) White	3 Participants n=5 Participants	7 Participants n=7 Participants	3 Participants n=5 Participants	7 Participants n=4 Participants	20 Participants n=21 Participants
Race (NIH/OMB) More than one race	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants	0 Participants n=4 Participants	0 Participants n=21 Participants
Region of Enrollment United States	12 participants n=5 Participants	12 participants n=7 Participants	11 participants n=5 Participants	11 participants n=4 Participants	46 participants n=21 Participants

PRIMARY outcome

Timeframe: prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion

Outcome measures

Measure	NAC Maternal n=11 Participants Mothers treated with N-acetylcysteine prior to delivery of infant	NAC Preterm Infants n=7 Participants Preterm infants treated with N-acetylcysteine	NAC Term Infants n=5 Participants Term infants treated with N-acetylcysteine	Control Maternal Mothers treated with saline prior to delivery
NAC Terminal Elimination Half-life	1.2 hours Standard Deviation 0.2	7.5 hours Standard Deviation 2.0	5.1 hours Standard Deviation 1.3	—

PRIMARY outcome

Timeframe: prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion

Outcome measures

Measure	NAC Maternal n=11 Participants Mothers treated with N-acetylcysteine prior to delivery of infant	NAC Preterm Infants n=7 Participants Preterm infants treated with N-acetylcysteine	NAC Term Infants n=5 Participants Term infants treated with N-acetylcysteine	Control Maternal Mothers treated with saline prior to delivery
NAC Volume of Distribution	0.41 L/kg Standard Deviation 0.07	0.47 L/kg Standard Deviation 0.04	0.38 L/kg Standard Deviation 0.09	—

PRIMARY outcome

Timeframe: prior to delivery in mothers, and in newborn after delivery during 2 days of NAC infusion

Outcome measures

Measure	NAC Maternal n=11 Participants Mothers treated with N-acetylcysteine prior to delivery of infant	NAC Preterm Infants n=7 Participants Preterm infants treated with N-acetylcysteine	NAC Term Infants n=5 Participants Term infants treated with N-acetylcysteine	Control Maternal Mothers treated with saline prior to delivery
NAC Total Body Clearance	255 mL/h/kg Standard Deviation 61	45.0 mL/h/kg Standard Deviation 8.2	53.7 mL/h/kg Standard Deviation 11.3	—

PRIMARY outcome

Timeframe: Peak: 30 minutes after NAC infusion. Cord: at delivery

Outcome measures

Measure	NAC Maternal n=11 Participants Mothers treated with N-acetylcysteine prior to delivery of infant	NAC Preterm Infants n=7 Participants Preterm infants treated with N-acetylcysteine	NAC Term Infants n=5 Participants Term infants treated with N-acetylcysteine	Control Maternal Mothers treated with saline prior to delivery
NAC Concentrations Peak NAC concentration in plasma	1222 micromol/L Standard Deviation 415	49.0 micromol/L Standard Deviation 14.9	92.3 micromol/L Standard Deviation 69.2	—
NAC Concentrations NAC cord concentration	NA micromol/L Standard Deviation NA Not applicable to mothers	370.7 micromol/L Standard Deviation 199.2	639.7 micromol/L Standard Deviation 409.4	—

PRIMARY outcome

Timeframe: At time of delivery

Ratio of NAC concentration in cord to maternal venous blood

Outcome measures

Measure	NAC Maternal n=12 Participants Mothers treated with N-acetylcysteine prior to delivery of infant	NAC Preterm Infants Preterm infants treated with N-acetylcysteine	NAC Term Infants Term infants treated with N-acetylcysteine	Control Maternal Mothers treated with saline prior to delivery
Placental Transfer Ratio	1.4 ratio Standard Deviation 0.8	—	—	—

PRIMARY outcome

Timeframe: Maternal mean BP changes were pre/post dosing prior to delivery. Infant measurements were pre/post their first dosing

Population: 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.

Outcome measures

Measure	NAC Maternal n=10 Participants Mothers treated with N-acetylcysteine prior to delivery of infant	NAC Preterm Infants n=7 Participants Preterm infants treated with N-acetylcysteine	NAC Term Infants n=11 Participants Term infants treated with N-acetylcysteine	Control Maternal n=10 Participants Mothers treated with saline prior to delivery
Maternal and Infant Mean Blood Pressure Change	-1.2 mmHg Standard Deviation 13	2.1 mmHg Standard Deviation 11	1 mmHg Standard Deviation 12	2 mmHg Standard Deviation 10

PRIMARY outcome

Timeframe: after NAC infusion

Population: blood flow resistive indices after first dose of N-acetylcysteine or saline

Resistive index in middle cerebral artery (MCA)

Outcome measures

Measure	NAC Maternal n=5 Participants Mothers treated with N-acetylcysteine prior to delivery of infant	NAC Preterm Infants n=4 Participants Preterm infants treated with N-acetylcysteine	NAC Term Infants n=6 Participants Term infants treated with N-acetylcysteine	Control Maternal n=5 Participants Mothers treated with saline prior to delivery
Cerebral Blood Flow	0.93 units on a scale Interval 0.87 to 0.99	0.89 units on a scale Interval 0.81 to 0.97	0.92 units on a scale Interval 0.88 to 0.97	0.89 units on a scale Interval 0.82 to 0.95

PRIMARY outcome

Timeframe: after N-acetylcystiene or saline infusion

prothrombin clotting time

Outcome measures

Measure	NAC Maternal n=8 Participants Mothers treated with N-acetylcysteine prior to delivery of infant	NAC Preterm Infants n=6 Participants Preterm infants treated with N-acetylcysteine	NAC Term Infants n=11 Participants Term infants treated with N-acetylcysteine	Control Maternal n=11 Participants Mothers treated with saline prior to delivery
Prothrombin Time	19.5 seconds Standard Deviation 2.5	19.0 seconds Standard Deviation 4.0	14.2 seconds Standard Deviation 0.6	14.4 seconds Standard Deviation 1.2

SECONDARY outcome

Timeframe: 36 - 40 weeks gestational age

ratio of myoInositol / NAA concentrations in basal ganglia

Outcome measures

Measure	NAC Maternal n=7 Participants Mothers treated with N-acetylcysteine prior to delivery of infant	NAC Preterm Infants n=9 Participants Preterm infants treated with N-acetylcysteine	NAC Term Infants Term infants treated with N-acetylcysteine	Control Maternal Mothers treated with saline prior to delivery
Magnetic Resonance Spectroscopy of Infants	1.09 ratio Standard Deviation 0.31	1.34 ratio Standard Deviation 0.20	—	—

SECONDARY outcome

Timeframe: after N-acetylcysteine infusion

anti-inflammatory cytokine Interleukin -1 Receptor alpha (IL-1Ra)

Outcome measures

Measure	NAC Maternal n=12 Participants Mothers treated with N-acetylcysteine prior to delivery of infant	NAC Preterm Infants n=9 Participants Preterm infants treated with N-acetylcysteine	NAC Term Infants Term infants treated with N-acetylcysteine	Control Maternal Mothers treated with saline prior to delivery
Cytokine Level IL-1Ra in Plasma	745 pg/ml Interval 251.0 to 1302.0	8.3 pg/ml Interval 8.3 to 448.0	—	—

Adverse Events

NAC Infant

Serious events: 4 serious events

Other events: 5 other events

Deaths: 0 deaths

Control Infant

Serious events: 3 serious events

Other events: 3 other events

Deaths: 0 deaths

NAC Maternal

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Control Maternal

Serious events: 0 serious events

Other events: 2 other events

Deaths: 0 deaths

Serious adverse events

Measure	NAC Infant n=12 participants at risk Infants treated with N-acetylcysteine	Control Infant n=12 participants at risk Infants treated with saline	NAC Maternal n=11 participants at risk Mothers of infants treated with N-acetylcysteine	Control Maternal n=11 participants at risk Mothers of infants treated with saline
General disorders Death	0.00% 0/12 • 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.	8.3% 1/12 • Number of events 1 • 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.	0.00% 0/11 • 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.	0.00% 0/11 • 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.
Nervous system disorders IVH 1-2 days of age	8.3% 1/12 • Number of events 1 • 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.	8.3% 1/12 • Number of events 1 • 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.	0.00% 0/11 • 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.	0.00% 0/11 • 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.
Nervous system disorders IVH 5-7 days of age	16.7% 2/12 • Number of events 2 • 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.	0.00% 0/12 • 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.	0.00% 0/11 • 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.	0.00% 0/11 • 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.
Nervous system disorders NEC within 30 days	8.3% 1/12 • Number of events 1 • 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.	8.3% 1/12 • Number of events 1 • 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.	0.00% 0/11 • 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.	0.00% 0/11 • 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.
Immune system disorders Pneumonia	8.3% 1/12 • Number of events 1 • 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.	0.00% 0/12 • 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.	0.00% 0/11 • 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.	0.00% 0/11 • 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.
Nervous system disorders Hypoxic Ischemic Encephalopathy	8.3% 1/12 • Number of events 1 • 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.	0.00% 0/12 • 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.	0.00% 0/11 • 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.	0.00% 0/11 • 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.
Immune system disorders Culture Proven Sepsis	8.3% 1/12 • Number of events 1 • 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.	8.3% 1/12 • Number of events 1 • 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.	0.00% 0/11 • 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.	0.00% 0/11 • 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.

Other adverse events

Measure	NAC Infant n=12 participants at risk Infants treated with N-acetylcysteine	Control Infant n=12 participants at risk Infants treated with saline	NAC Maternal n=11 participants at risk Mothers of infants treated with N-acetylcysteine	Control Maternal n=11 participants at risk Mothers of infants treated with saline
Skin and subcutaneous tissue disorders Rash/Hives	0.00% 0/12 • 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.	0.00% 0/12 • 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.	9.1% 1/11 • Number of events 1 • 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.	0.00% 0/11 • 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.
Respiratory, thoracic and mediastinal disorders Shortness of breath/wheezing	0.00% 0/12 • 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.	0.00% 0/12 • 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.	0.00% 0/11 • 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.	9.1% 1/11 • Number of events 1 • 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.
Blood and lymphatic system disorders Hypotension	0.00% 0/12 • 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.	8.3% 1/12 • Number of events 1 • 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.	9.1% 1/11 • Number of events 1 • 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.	9.1% 1/11 • Number of events 1 • 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.
Blood and lymphatic system disorders Prolonged PT time	62.5% 5/8 • Number of events 5 • 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.	50.0% 3/6 • Number of events 3 • 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.	0.00% 0/11 • 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.	0.00% 0/11 • 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.

Additional Information

Dr. Dorothea Jenkins

Medical University of South Carolina

Phone: 843-792-4341

Email: jenkd@musc.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place