Preterm DeliveryPhase 4ACSNCT00201643
A Randomized Trial Comparing the Impact of One Versus Two Courses of Antenatal Steroids (ACS) on Neonatal Outcome
A Phase 4 study testing Betamethasone or Dexamethasone (2nd course of ACS) in people with Preterm Delivery, run by Obstetrix Medical Group at 22 sites in United States.
Trial summary
The hypothesis is that administration of two courses of antenatal corticosteroids, compared to one course, will show a 40% reduction in the incidence of composite neonatal morbidity in patients delivering prior to 34 weeks' gestation. Read more about this study
- Who is it for?
- Ages 18 to 60 years, women only
- Conditions the study is for
- Preterm Delivery
- What is being tested?
- Betamethasone or Dexamethasone (2nd course of ACS)
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 437 participants
- Where
- 22 sitesUnited States
- Study dates
- Nov 2003to Feb 2008
- Phase
- Phase 4
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 to 60 years
- Women only
- No healthy volunteers
- Adult
Who may be able to join
- 25 to 32 6/7 weeks gestation
- Singleton or twin gestation
- Received 1st course of betamethasone prior to 30 weeks' gestation
- Began 1st course of betamethasone at least 14 days prior to randomization
- Risk of delivery in next 7 days due to either maternal or fetal complication (e.g. preterm labor, severe preeclampsia, IUGR, etc.)
- Intact membranes
Who cannot join
- Known major fetal anomalies (eg: anencephaly, renal agenesis etc…)
- High order multiple gestation (triplets or higher)
- Cervical dilation > 5 cm
- Clinical chorioamnionitis prior to initiation of second course (two or more of the following; antepartum temperature > 38ºC (100.4ºF), uterine tenderness, foul smelling vaginal discharge or amniotic fluid, maternal tachycardia (>100beats/min), fetal tachycardia (>160 beats/min), or white blood cell count >20x109/L.define)
- Ruptured membranes prior to initiation of second course of betamethasone
- Already receiving corticosteroids for other conditions (e.g. Lupus, asthma)
- Maternal condition contraindicating the use of steroids (e.g. HIV, active Tuberculosis)
- Participation in conflicting study
Trial locations and contacts
22 sites in 1 country.
22 sites in 1 country
United States22 sites
Tufts-New England Medical Center
Boston, Massachusetts, 02111
Erlanger Medical Center
Chattanooga, Tennessee, 37403
Swedish Medical Center
Denver, Colorado, 80110
Presbyterian/St Luke's Hospital
Denver, Colorado, 80218
Rose Medical Center
Denver, Colorado, 80220
Mercy Medical Center
Des Moines, Iowa, 50314
Saint Luke's Hospital, Kansas City
Kansas City, Missouri, 64111
Evergreen Hospital
Kirkland, Washington, 98034
University of Tennessee Medical Center
Knoxville, Tennessee, 37920
Saddleback Memorial Medical Center
Laguna Hills, California, 92653
University Med. Ctr. of Southern Nevada
Las Vegas, Nevada, 89102
Sunrise Medical Center
Las Vegas, Nevada, 89109
Skyridge Medical Center
Lonetree, Colorado, 80124
Long Beach Memorial Medical Center
Long Beach, California, 90801-1428
Desert Good Samaritan Hospital
Mesa, Arizona, 85202
University of Sourthern California-Irvine Medical Center
Orange, California, 92868
Banner Good Sammaritan Hospital
Phoenix, Arizona, 85006
University of Utah Health Sciences Center
Salt Lake City, Utah, 84132
Good Samaritan Hospital
San Jose, California, 95124
Swedish Medical Center
Seattle, Washington, 98122-4307
Saint John's Regional Health Center
Springfield, Missouri, 65804
Tucson Medical Center
Tucson, Arizona, 85712
About this study
Official title: A Randomized Double-Blinded Study Comparing the Impact of One Versus Two Courses of Antenatal Steroids on Neonatal Outcome
The hypothesis is that administration of two courses of antenatal corticosteroids, compared to one course, will show a 40% reduction in the incidence of composite neonatal morbidity in patients delivering prior to 34 weeks' gestation.
Read the detailed description
This is a randomized double-blinded placebo-controlled trial. The objective of this study is to evaluate the impact of one versus two courses of antenatal steroids on the incidence of major neonatal morbidity including respiratory distress syndrome in patients delivering prior to 34 weeks' gestation in a randomized prospective fashion.
Preterm delivery occurs in approximately 10% of all deliveries in the United States. Preterm birth is the cause of 75% of neonatal mortality not mentioning the significantly increased morbidity from respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and sepsis. Numerous studies have evaluated the safety and efficacy of antenatal corticosteroid (ACS) administration in threatened preterm labor.
National Institutes of Health (NIH) first consensus conference in 1994 evaluated the research in this field. Conclusions included the clear evidence that antenatal corticosteroids decrease the incidence of RDS in infants born at 29-34 weeks gestation, with a decrease in RDS severity for infants born at 24-28 weeks gestation and a decrease in the incidence of intraventricular hemorrhage in infants born at 24-28 weeks gestation without harm to mother or fetus. Their recommendation was to give a single course of corticosteroids to all pregnant women between 24 and 34 weeks gestation who are at risk of preterm delivery within 7 days.
Since the studies on the duration of the effects of antenatal corticosteroids in the fetus are not conclusive, many obstetricians repeat corticosteroids weekly or bi-weekly to patients continuing to be at risk for preterm delivery. Lacking scientific evidence, many investigators have performed retrospective analyses regarding the effects of single-course versus multiple-course antenatal corticosteroids.
The NIH consensus panel reconvened in 2000 and concluded that studies regarding repeated courses of corticosteroids are suggestive of possible benefits, especially in reduction of RDS, however, design flaws limit their validity.
The more recent publication from Caughey and Parer examined the literature for evidence regarding a dose response of the benefits and detriments of antenatal corticosteroids. Based on their complex mathematical analysis they recommend all fetus' between 24 and 34 weeks' gestation at risk for preterm delivery should be given a first course of ANC. If the risk of preterm delivery persists the next course should be given 2 weeks later, for a maximum of two courses. Consistent with all previous articles, the call for a well designed randomized, controlled trial is made.
- Conditions
- Preterm Delivery
- Being tested
- Betamethasone or Dexamethasone (2nd course of ACS), Placebo
- Keywords
- Preterm Labor, Preterm delivery
- Medical subject headings
- Premature Birth, Obstetric Labor, Premature
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Betamethasone or Dexamethasone (2nd course of ACS)Drug
Also called Beta, Dex
Course of Betamethasone or Dexamethasone
PlaceboDrug
Also called Placebo, Normal Saline.
Course of Placebo (NS)
| Study group | Role | What they receive |
|---|---|---|
| 1 Test group | Active comparator | Receive 2nd Course = Study drug (betamethasone or dexamethasone) Receives: Drug: Betamethasone or Dexamethasone (2nd course of ACS) |
| 2 - Control | Placebo comparator | Placebo group = received placebo course Receives: Drug: Placebo |
What is being measured
The primary outcome is the main question the study is designed to answer.
Composite Neonatal Morbidity < 34 Weeks Gestation at Time of Birth.
This outcome measured the total number of neonates with Composite Neonatal morbidity who delivered at < 34 weeks gestation. Composite Morbidity consisted of respiratory distress syndrome, bronchopulmonary dysplasia, severe intraventricular hemorrhage, periventricular leukomalacia, proven sepsis, necrotizing enterocolitis, or perinatal death
Measured: From birth to 28 days of life
Secondary outcomes (8)
Gestational Age at (@) Delivery
Reported the average/mean Neonatal gestational age (GA) (reported in weeks of pregnancy) at the time of birth for both groups (ACS vs. Placebo).
Measured: gestational age at delivery in weeks of gestation
Neonatal Birth Weight Reported in Grams
Measured mean Birth weights of Neonates in each arm as reported in grams on the birth record.
Measured: At time of Birth
Interuterine Growth Restriction (IUGR) or Small for Gestational Age(SGA)in Babies Delivering at < 34 Weeks Gestation.
Noted as the total number of Neonates delivering at < 34 weeks gestation for which their weights fell within the 10th percentile at time of birth.
Measured: Measured at birth.
Neonatal Head Circumference Taken at Time of Birth.
Reported as the average of all neonatal head circumferences (HC) taken at time of birth in each group.
Measured: Birth
Number of Babies Who Required Ventilatory Support Within the First 28 Days of Life.
The number of babies who required ventilatory support within the first 28 days of life. Equal to or great than 12 hours was considered one day.
Measured: birth to 28 days of life
Number of Neonates Who Required Surfactant Therapy After Birth.
The Number of neonates who required surfactant therapy within the first 28 days after birth.
Measured: Birth to 28 days of life
Number of Neonates With Pneumothorax
Total number of neonates with pneumothorax diagnosed postpartum.
Measured: birth to 28 days of life
Maternal Infectious Morbidity.
Total number of Mothers having Maternal infectious morbidity (e.g. endometritis \& maternal sepsis) noted from birth through 28 days after birth
Measured: Up to 28 days after giving birth
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted20 Sep 2005 (estimated)
- Study startNov 2003
- Primary completionFeb 2008
- Study completionFeb 2008
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (5)Papers the sponsor has linked to this study.
- Other trials for Preterm DeliveryStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 437 participants (actual)
Sponsor and investigators
- Lead sponsor
- Obstetrix Medical Group
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Kimberly Maurel, RN, MSN, CNS, Study director, Obstetrix Medical Group, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00201643
- Sponsor's protocol ID
- OBX0001
- Other IDs
- OBX0001
- Acronym
- ACS
- Status last verified
- Dec 2014
- First submitted
- 12 Sep 2005
- Last updated
- 7 Jan 2015
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
Publications
Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consens Statement. 1994 Feb 28-Mar 2;12(2):1-24.
PubMed 7728157Vermillion ST, Soper DE, Newman RB. Is betamethasone effective longer than 7 days after treatment? Obstet Gynecol. 2001 Apr;97(4):491-3. doi: 10.1016/s0029-7844(00)01178-9.
PubMed 11275015Antenatal corticosteroids revisited: repeat courses. NIH Consens Statement. 2000 Aug 17-18;17(2):1-18.
PubMed 11725806Guinn DA, Atkinson MW, Sullivan L, Lee M, MacGregor S, Parilla BV, Davies J, Hanlon-Lundberg K, Simpson L, Stone J, Wing D, Ogasawara K, Muraskas J. Single vs weekly courses of antenatal corticosteroids for women at risk of preterm delivery: A randomized controlled trial. JAMA. 2001 Oct 3;286(13):1581-7. doi: 10.1001/jama.286.13.1581.
PubMed 11585480Caughey AB, Parer JT. Recommendations for repeat courses of antenatal corticosteroids: a decision analysis. Am J Obstet Gynecol. 2002 Jun;186(6):1221-6; discussion 1226-9. doi: 10.1067/mob.2002.123742.
PubMed 12066102
Study at a glance
From the registry record, last updated by the sponsor on 7 Jan 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Randomized Double-Blinded Study Comparing the Impact of One Versus Two Courses of Antenatal Steroids on Neonatal Outcome
- ClinicalTrials.gov ID
- NCT00201643
- Acronym / sponsor ID
- ACS / OBX0001
- Conditions
- Preterm Delivery
- Keywords
- Preterm Labor, Preterm delivery
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 437 participants (actual)
- Lead sponsor
- Obstetrix Medical GroupIndustry (pharma, biotech, devices)
- Study start
- Nov 2003
- Primary completion
- Feb 2008 (actual)
- Study completion
- Feb 2008 (actual)
- First posted
- 20 Sep 2005 (estimated)
- Results
- Posted 1 Mar 2011
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The hypothesis is that administration of two courses of antenatal corticosteroids, compared to one course, will show a 40% reduction in the incidence of composite neonatal morbidity in patients delivering prior to 34 weeks' gestation.
Detailed description
This is a randomized double-blinded placebo-controlled trial. The objective of this study is to evaluate the impact of one versus two courses of antenatal steroids on the incidence of major neonatal morbidity including respiratory distress syndrome in patients delivering prior to 34 weeks' gestation in a randomized prospective fashion.
Preterm delivery occurs in approximately 10% of all deliveries in the United States. Preterm birth is the cause of 75% of neonatal mortality not mentioning the significantly increased morbidity from respiratory distress syndrome, intraventricular hemorrhage, necrotizing enterocolitis, and sepsis. Numerous studies have evaluated the safety and efficacy of antenatal corticosteroid (ACS) administration in threatened preterm labor.
National Institutes of Health (NIH) first consensus conference in 1994 evaluated the research in this field. Conclusions included the clear evidence that antenatal corticosteroids decrease the incidence of RDS in infants born at 29-34 weeks gestation, with a decrease in RDS severity for infants born at 24-28 weeks gestation and a decrease in the incidence of intraventricular hemorrhage in infants born at 24-28 weeks gestation without harm to mother or fetus. Their recommendation was to give a single course of corticosteroids to all pregnant women between 24 and 34 weeks gestation who are at risk of preterm delivery within 7 days.
Since the studies on the duration of the effects of antenatal corticosteroids in the fetus are not conclusive, many obstetricians repeat corticosteroids weekly or bi-weekly to patients continuing to be at risk for preterm delivery. Lacking scientific evidence, many investigators have performed retrospective analyses regarding the effects of single-course versus multiple-course antenatal corticosteroids.
The NIH consensus panel reconvened in 2000 and concluded that studies regarding repeated courses of corticosteroids are suggestive of possible benefits, especially in reduction of RDS, however, design flaws limit their validity.
The more recent publication from Caughey and Parer examined the literature for evidence regarding a dose response of the benefits and detriments of antenatal corticosteroids. Based on their complex mathematical analysis they recommend all fetus' between 24 and 34 weeks' gestation at risk for preterm delivery should be given a first course of ANC. If the risk of preterm delivery persists the next course should be given 2 weeks later, for a maximum of two courses. Consistent with all previous articles, the call for a well designed randomized, controlled trial is made.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1 Test group | Active comparator | Drug: Betamethasone or Dexamethasone (2nd course of ACS)Receive 2nd Course = Study drug (betamethasone or dexamethasone) |
| 2 - Control | Placebo comparator | Drug: PlaceboPlacebo group = received placebo course |
Who may qualify
- Ages
- 18 to 60 years
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult
Key inclusion criteria (6 listed)
- 25 to 32 6/7 weeks gestation
- Singleton or twin gestation
- Received 1st course of betamethasone prior to 30 weeks' gestation
- Began 1st course of betamethasone at least 14 days prior to randomization
- Risk of delivery in next 7 days due to either maternal or fetal complication (e.g. preterm labor, severe preeclampsia, IUGR, etc.)
Key exclusion criteria (8 listed)
- Known major fetal anomalies (eg: anencephaly, renal agenesis etc…)
- High order multiple gestation (triplets or higher)
- Cervical dilation > 5 cm
- Clinical chorioamnionitis prior to initiation of second course (two or more of the following; antepartum temperature > 38ºC (100.4ºF), uterine tenderness, foul smelling vaginal discharge or amniotic fluid, maternal tachycardia (>100beats/min), fetal tachycardia (>160 beats/min), or white blood cell count >20x109/L.define)
- Ruptured membranes prior to initiation of second course of betamethasone
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 |
|---|---|---|
| Betamethasone or Dexamethasone (2nd course of ACS)Also: Beta, DexCourse of Betamethasone or Dexamethasone | Drug | 1 Test group |
| PlaceboAlso: Placebo, Normal Saline.Course of Placebo (NS) | Drug | 2 - Control |
Primary outcome
Composite Neonatal Morbidity < 34 Weeks Gestation at Time of Birth.
Time frame: From birth to 28 days of life
This outcome measured the total number of neonates with Composite Neonatal morbidity who delivered at < 34 weeks gestation. Composite Morbidity consisted of respiratory distress syndrome, bronchopulmonary dysplasia, severe intraventricular hemorrhage, periventricular leukomalacia, proven sepsis, necrotizing enterocolitis, or perinatal death
8 secondary outcomes
Gestational Age at (@) Delivery
Time frame: gestational age at delivery in weeks of gestation
Neonatal Birth Weight Reported in Grams
Time frame: At time of Birth
Interuterine Growth Restriction (IUGR) or Small for Gestational Age(SGA)in Babies Delivering at < 34 Weeks Gestation.
Time frame: Measured at birth.
Neonatal Head Circumference Taken at Time of Birth.
Time frame: Birth
Number of Babies Who Required Ventilatory Support Within the First 28 Days of Life.
Time frame: birth to 28 days of life
Number of Neonates Who Required Surfactant Therapy After Birth.
Time frame: Birth to 28 days of life
Number of Neonates With Pneumothorax
Time frame: birth to 28 days of life
Maternal Infectious Morbidity.
Time frame: Up to 28 days after giving birth
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Jan 2015.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Background: PubMed 7728157Effect of corticosteroids for fetal maturation on perinatal outcomes. NIH Consens Statement. 1994 Feb 28-Mar 2;12(2):1-24.
- Background: PubMed 11275015Vermillion ST, Soper DE, Newman RB. Is betamethasone effective longer than 7 days after treatment? Obstet Gynecol. 2001 Apr;97(4):491-3. doi: 10.1016/s0029-7844(00)01178-9.
- Background: PubMed 11725806Antenatal corticosteroids revisited: repeat courses. NIH Consens Statement. 2000 Aug 17-18;17(2):1-18.
- Background: PubMed 11585480Guinn DA, Atkinson MW, Sullivan L, Lee M, MacGregor S, Parilla BV, Davies J, Hanlon-Lundberg K, Simpson L, Stone J, Wing D, Ogasawara K, Muraskas J. Single vs weekly courses of antenatal corticosteroids for women at risk of preterm delivery: A randomized controlled trial. JAMA. 2001 Oct 3;286(13):1581-7. doi: 10.1001/jama.286.13.1581.
- Background: PubMed 12066102Caughey AB, Parer JT. Recommendations for repeat courses of antenatal corticosteroids: a decision analysis. Am J Obstet Gynecol. 2002 Jun;186(6):1221-6; discussion 1226-9. doi: 10.1067/mob.2002.123742.
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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.
Kimberly Maurel, RN, MSN, CNS study director
Obstetrix Medical Group, Inc.
22 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Betamethasone or Dexamethasone (2nd course of ACS) in people with Preterm Delivery, run by Obstetrix Medical Group at 22 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 6 inclusion and 8 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 7 Jan 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 22 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 phase mean?
Phase 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 1 Mar 2011). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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 Neonatal Morbidity < 34 Weeks Gestation at Time of Birth. (time frame: From birth to 28 days of life). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT00201643, which also lists 5 linked publications.
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 7 Jan 2015.