Labor, PrematurePhase 1/2NCT00397735
N-acetylcysteine in Intra-amniotic Infection/Inflammation
A Phase 1/2 study testing amniocentesis in people with Labor, Premature and Preterm Premature Rupture of the Membranes, run by Ohio State University at 2 sites in United States.
Trial 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). Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Labor, Premature, Preterm Premature Rupture of the Membranes, Infection
- What is being tested?
- amniocentesis
- Type of treatment
- Injection or infusion, Surgery or procedure
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 68 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Oct 2006to 1 Aug 2018
- Phase
- Phase 1/2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- Women only
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- 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.
Who cannot join
- 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
Trial locations and contacts
2 sites in 1 country.
United States2 sites
The Research Institute at Nationwide Children's Hospital
Columbus, Ohio, 43215
Yale New Haven Hospital
New Haven, Connecticut, 06510
About this study
Official title: Effect of N-acetylcysteine in Preventing Adverse Neonatal Outcomes in Women With Intra-amniotic Infection/Inflammation
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.
Read the 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
- Conditions
- Labor, Premature, Preterm Premature Rupture of the Membranes, Infection, Inflammation, Chorioamnionitis
- Being tested
- amniocentesis, N-acetylcysteine or placebo
- Keywords
- pregnancy, chorioamnionitis, preterm labor, preterm premature rupture of the membranes, Intra-amniotic infection, Intra-amniotic inflammation
- Medical subject headings
- Obstetric Labor, Premature, Preterm Premature Rupture of the Membranes, Infections, Inflammation, Chorioamnionitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
amniocentesisProcedure or surgery
Also called transabdominal 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.
N-acetylcysteine or placeboDrug
Also called Mucomyst, Acetadote
Only women with amniocentesis results consistent with infection/inflammation will be randomized
| Study group | Role | What they receive |
|---|---|---|
| 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. Receives: 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 Receives: Procedure: amniocentesis; Drug: N-acetylcysteine or placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
composite of mortality and severe short term neonatal morbidities (IVH, NEC, BPD, ROP, sepsis, newborn death)
IVH, NEC, BPD, ROP, Sepsis, death
Measured: up to 1 year
Secondary outcomes (6)
neonatal sepsis
early and late neonatal sepsis
Measured: up to 30 days
maternal and umbilical cord plasma antioxidant capacity
plasma antioxidant capacity
Measured: up to 1 day
maternal and umbilical cord plasma N-acetylcysteine levels
N-acetylcysteine levels
Measured: up to 1 day
umbilical cord levels of inflammatory cytokine concentrations
pannel of pro and anti inflammatory cytokines
Measured: up to 1 day
funisitis grades
histology
Measured: up to 1 day
maternal and umbilical cord blood glutathione concentration
glutathione levels
Measured: up to 1 day
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted9 Nov 2006 (estimated)
- Study start1 Oct 2006
- Primary completion29 Oct 2012
- Study completion1 Aug 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Labor, PrematureStudies of the same condition, open and under way.
- More trials run by Ohio State UniversityThe sponsor's other registered studies.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 1/2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 68 participants (actual)
Sponsor and investigators
- Lead sponsor
- Ohio State University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Catalin S Buhimschi, MD, Ohio State University
- Investigators
- Catalin S Buhimschi, MD, MBA, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00397735
- Sponsor's protocol ID
- 0603001228
- Status last verified
- Oct 2018
- First submitted
- 7 Nov 2006
- Last updated
- 10 Oct 2018
- Results posted
- No
- Data monitoring committee
- No
Study at a glance
From the registry record, last updated by the sponsor on 10 Oct 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Effect of N-acetylcysteine in Preventing Adverse Neonatal Outcomes in Women With Intra-amniotic Infection/Inflammation
- ClinicalTrials.gov ID
- NCT00397735
- Acronym / sponsor ID
- 0603001228
- 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
- Phase
- Phase 1/2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 68 participants (actual)
- Lead sponsor
- Ohio State UniversityUniversity, hospital or other
- Study start
- 1 Oct 2006
- Primary completion
- 29 Oct 2012 (actual)
- Study completion
- 1 Aug 2018 (actual)
- First posted
- 9 Nov 2006 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
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.
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 design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| N-Acetylcysteine | Experimental | Procedure: amniocentesis, Drug: N-acetylcysteine or placeboThe 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. |
| Placebo | Placebo comparator | Procedure: amniocentesis, Drug: N-acetylcysteine or placeboThe 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 |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- 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.
Key exclusion criteria (1 listed)
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| amniocentesisAlso: transabdominal amniocentesisAmniotic 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. | Procedure or surgery | N-Acetylcysteine, Placebo |
| N-acetylcysteine or placeboAlso: Mucomyst, AcetadoteOnly women with amniocentesis results consistent with infection/inflammation will be randomized | Drug | N-Acetylcysteine, Placebo |
Primary outcome
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
6 secondary outcomes
neonatal sepsis
Time frame: up to 30 days
maternal and umbilical cord plasma antioxidant capacity
Time frame: up to 1 day
maternal and umbilical cord plasma N-acetylcysteine levels
Time frame: up to 1 day
umbilical cord levels of inflammatory cytokine concentrations
Time frame: up to 1 day
funisitis grades
Time frame: up to 1 day
maternal and umbilical cord blood glutathione concentration
Time frame: up to 1 day
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 10 Oct 2018.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Catalin S Buhimschi, MD, MBA principal investigator
Ohio State University
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1/2 study testing amniocentesis in people with Labor, Premature and Preterm Premature Rupture of the Membranes, run by Ohio State University at 2 sites in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 1 inclusion and 1 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 10 Oct 2018. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. Some participants in this study may receive a placebo. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
composite of mortality and severe short term neonatal morbidities (IVH, NEC, BPD, ROP, sepsis, newborn death) (time frame: up to 1 year). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 10 Oct 2018.