Preterm Premature Rupture of MembraneNCT05328817
Azithromycin Versus Erythromycin For Preterm Prelabor Rupture of Membranes
A study testing Antibiotics in people with Preterm Premature Rupture of Membrane, run by Eastern Virginia Medical School.
Trial summary
Aim 1. To examine the latency period according to antibiotic regimens (erythromycin iv for two days followed by orally for 5 days vs. azithromycin iv for 2 days followed by 5 days orally). Aim 2. To examine the latency period according to races stratified by antibiotic regimens. Read more about this study
- Who is it for?
- Ages 18 to 50 years, women onlyHealthy volunteers can take part
- Conditions the study is for
- Preterm Premature Rupture of Membrane
- What is being tested?
- Antibiotics
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 240 participants
- Where
- No sites listed yet
- Study dates
- 1 May 2022to 1 Jul 2025
- Phase
- Interventional
- 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 to 50 years
- Women only
- Healthy volunteers accepted
- Adult
Who may be able to join
- Singleton pregnancy
- PPROM from 22 weeks 0 days to 31 weeks 6 days at Sentara Norfolk General Hospital
- Membrane rupture within 36 hours of randomization, cervical dilation 3 cm or less, and 4 or fewer contractions in the 60-minutes monitoring before randomization
Who cannot join
- Non-reassuring fetal heart tracing
- Vaginal bleeding
- Indications for delivery
- Received any antibiotic therapy within 7 days other than initiation of Ampicillin treatment as part of latency antibiotics prior to transfer to Sentara Norfolk General Hospital
- Allergy to penicillin, erythromycin, or azithromycin
Trial locations and contacts
No sites are listed yet.
About this study
Official title: Azithromycin Versus Erythromycin For Preterm Prelabor Rupture of Membranes: A Randomized Controlled Trial
Aim 1. To examine the latency period according to antibiotic regimens (erythromycin iv for two days followed by orally for 5 days vs. azithromycin iv for 2 days followed by 5 days orally).
Aim 2. To examine the latency period according to races stratified by antibiotic regimens.
Aim 3: To examine if there is a difference in neonatal morbidity and mortality stratified by antibiotic regimen.
Read the detailed description
Significant differences exist in the pharmacokinetics and pharmacodynamics pathways of macrolide antibiotics between different races and ethnicities. Erythromycin compared to azithromycin interacts with more proteins and is likely affected by genetic variation. Therefore, the investigators hypothesize that the optimal latency antibiotic regimens for PPROM could potentially differ between races.
Due to the paucity of data regarding the use of an azithromycin regimen for latency antibiotics, the Eastern Virginia Medical School MFM team uses an erythromycin regimen even though azithromycin requires less frequent dosing, has lower rates of side effects, and is more cost effective. The Center for Maternal and Child Health Equity at Eastern Virginia Medical School was developed to address health disparities for mothers and their children, and the investigator team is committed to working with the center to address this research gap regarding latency antibiotic use in PPROM.
The aim is to determine the optimal antibiotic regimen for women with PPROM. The hypothesis to be tested are 1) The antibiotic regimen with azithromycin (iv for 2 days followed by 5 days orally) is associated with a longer latency period compared to the antibiotic regimen with erythromycin, and 2) The antibiotic regimen with azithromycin reduces disparity in latency period compared to the antibiotic regimen with erythromycin.
- Conditions
- Preterm Premature Rupture of Membrane
- Being tested
- Antibiotics
- Medical subject headings
- Preterm Premature Rupture of the Membranes
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
AntibioticsDrug
Also called Latency antibiotics, Broad-spectrum antibiotics
In the absence of labor, broad-spectrum antibiotics (often called latency antibiotics) are recommended for women with PPROM less than 34 weeks to reduce chorioamnionitis, prolong latency, and decrease neonatal sepsis (12,13).
| Study group | Role | What they receive |
|---|---|---|
| Erythromycin | Experimental | Receive 1) erythromycin 250 mg iv every 6 hours for 48 hours followed by 333 mg orally (pills) every 8 hours for 5 days Receives: Drug: Antibiotics |
| Azithromycin | Experimental | Receive azithromycin 500 mg iv daily for 48 hours followed by 500 mg orally (pills) for 5 days. Receives: Drug: Antibiotics |
What is being measured
The primary outcome is the main question the study is designed to answer.
Latency Period
The time interval between the first antibiotic dose to time of delivery.
Measured: At delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Apr 2022
- Study start1 May 2022 (estimated)
- Primary completion1 May 2025 (estimated)
- Study completion1 Jul 2025 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (24)Papers the sponsor has linked to this study.
- Other trials for Preterm Premature Rupture of MembraneStudies 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 N/A
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- In order to maintain balanced groups, block randomization will be used. Pregnant women will be randomized in blocks of 6 with a total number of blocks to be 40. This will be conducted using STATA16 software, which will generate random permutations of sequential IDs of eligible study participants and their assignment to the treatment arms. This will be transferred to the REDCap in which a database will be created to facilitate random assignment during recruitment while maintaining concealment of randomization.
- Masking
- None (open label)
- Enrolment
- 240 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Eastern Virginia Medical School
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Tetsuya Kawakita, MD, Principal investigator, Eastern Virginia Medical School
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT05328817
- Sponsor's protocol ID
- 22-01-FB-0001
- Status last verified
- Apr 2022
- First submitted
- 7 Apr 2022
- Last updated
- 14 Apr 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Waters TP, Mercer B. Preterm PROM: prediction, prevention, principles. Clin Obstet Gynecol. 2011 Jun;54(2):307-12. doi: 10.1097/GRF.0b013e318217d4d3.
PubMed 21508700Meis PJ, Ernest JM, Moore ML. Causes of low birth weight births in public and private patients. Am J Obstet Gynecol. 1987 May;156(5):1165-8. doi: 10.1016/0002-9378(87)90133-5.
PubMed 3578431Beydoun SN, Yasin SY. Premature rupture of the membranes before 28 weeks: conservative management. Am J Obstet Gynecol. 1986 Sep;155(3):471-9. doi: 10.1016/0002-9378(86)90257-7.
PubMed 3752169Garite TJ, Freeman RK. Chorioamnionitis in the preterm gestation. Obstet Gynecol. 1982 May;59(5):539-45.
PubMed 7070724Pergialiotis V, Bellos I, Fanaki M, Antsaklis A, Loutradis D, Daskalakis G. The impact of residual oligohydramnios following preterm premature rupture of membranes on adverse pregnancy outcomes: a meta-analysis. Am J Obstet Gynecol. 2020 Jun;222(6):628-630. doi: 10.1016/j.ajog.2020.02.022. Epub 2020 Feb 25. No abstract available.
PubMed 32109463Costeloe KL, Hennessy EM, Haider S, Stacey F, Marlow N, Draper ES. Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies). BMJ. 2012 Dec 4;345:e7976. doi: 10.1136/bmj.e7976.
PubMed 23212881Marlow N, Wolke D, Bracewell MA, Samara M; EPICure Study Group. Neurologic and developmental disability at six years of age after extremely preterm birth. N Engl J Med. 2005 Jan 6;352(1):9-19. doi: 10.1056/NEJMoa041367.
PubMed 15635108Averbuch B, Mazor M, Shoham-Vardi I, Chaim W, Vardi H, Horowitz S, Shuster M. Intra-uterine infection in women with preterm premature rupture of membranes: maternal and neonatal characteristics. Eur J Obstet Gynecol Reprod Biol. 1995 Sep;62(1):25-9. doi: 10.1016/0301-2115(95)02176-8.
PubMed 7493703Shen TT, DeFranco EA, Stamilio DM, Chang JJ, Muglia LJ. A population-based study of race-specific risk for preterm premature rupture of membranes. Am J Obstet Gynecol. 2008 Oct;199(4):373.e1-7. doi: 10.1016/j.ajog.2008.05.011. Epub 2008 Jul 29.
PubMed 18667175Drassinower D, Friedman AM, Obican SG, Levin H, Gyamfi-Bannerman C. Prolonged latency of preterm prelabour rupture of membranes and neurodevelopmental outcomes: a secondary analysis. BJOG. 2016 Sep;123(10):1629-35. doi: 10.1111/1471-0528.14133. Epub 2016 May 31.
PubMed 27245741Boghossian NS, Geraci M, Lorch SA, Phibbs CS, Edwards EM, Horbar JD. Racial and Ethnic Differences Over Time in Outcomes of Infants Born Less Than 30 Weeks' Gestation. Pediatrics. 2019 Sep;144(3):e20191106. doi: 10.1542/peds.2019-1106. Epub 2019 Aug 12.
PubMed 31405887Kenyon S, Boulvain M, Neilson JP. Antibiotics for preterm rupture of membranes. Cochrane Database Syst Rev. 2013 Dec 2;2013(12):CD001058. doi: 10.1002/14651858.CD001058.pub3.
PubMed 24297389Prelabor Rupture of Membranes: ACOG Practice Bulletin, Number 217. Obstet Gynecol. 2020 Mar;135(3):e80-e97. doi: 10.1097/AOG.0000000000003700.
PubMed 32080050Mercer BM, Moretti ML, Prevost RR, Sibai BM. Erythromycin therapy in preterm premature rupture of the membranes: a prospective, randomized trial of 220 patients. Am J Obstet Gynecol. 1992 Mar;166(3):794-802. doi: 10.1016/0002-9378(92)91336-9.
PubMed 1550145Mercer BM, Miodovnik M, Thurnau GR, Goldenberg RL, Das AF, Ramsey RD, Rabello YA, Meis PJ, Moawad AH, Iams JD, Van Dorsten JP, Paul RH, Bottoms SF, Merenstein G, Thom EA, Roberts JM, McNellis D. Antibiotic therapy for reduction of infant morbidity after preterm premature rupture of the membranes. A randomized controlled trial. National Institute of Child Health and Human Development Maternal-Fetal Medicine Units Network. JAMA. 1997 Sep 24;278(12):989-95.
PubMed 9307346
Study at a glance
From the registry record, last updated by the sponsor on 14 Apr 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Azithromycin Versus Erythromycin For Preterm Prelabor Rupture of Membranes: A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT05328817
- Acronym / sponsor ID
- 22-01-FB-0001
- Conditions
- Preterm Premature Rupture of Membrane
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 240 participants (estimated)
- Lead sponsor
- Eastern Virginia Medical SchoolUniversity, hospital or other
- Study start
- 1 May 2022 (estimated)
- Primary completion
- 1 May 2025 (estimated)
- Study completion
- 1 Jul 2025 (estimated)
- First posted
- 14 Apr 2022 (actual)
- 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.
Aim 1. To examine the latency period according to antibiotic regimens (erythromycin iv for two days followed by orally for 5 days vs. azithromycin iv for 2 days followed by 5 days orally).
Aim 2. To examine the latency period according to races stratified by antibiotic regimens.
Aim 3: To examine if there is a difference in neonatal morbidity and mortality stratified by antibiotic regimen.
Detailed description
Significant differences exist in the pharmacokinetics and pharmacodynamics pathways of macrolide antibiotics between different races and ethnicities. Erythromycin compared to azithromycin interacts with more proteins and is likely affected by genetic variation. Therefore, the investigators hypothesize that the optimal latency antibiotic regimens for PPROM could potentially differ between races.
Due to the paucity of data regarding the use of an azithromycin regimen for latency antibiotics, the Eastern Virginia Medical School MFM team uses an erythromycin regimen even though azithromycin requires less frequent dosing, has lower rates of side effects, and is more cost effective. The Center for Maternal and Child Health Equity at Eastern Virginia Medical School was developed to address health disparities for mothers and their children, and the investigator team is committed to working with the center to address this research gap regarding latency antibiotic use in PPROM.
The aim is to determine the optimal antibiotic regimen for women with PPROM. The hypothesis to be tested are 1) The antibiotic regimen with azithromycin (iv for 2 days followed by 5 days orally) is associated with a longer latency period compared to the antibiotic regimen with erythromycin, and 2) The antibiotic regimen with azithromycin reduces disparity in latency period compared to the antibiotic regimen with erythromycin.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- In order to maintain balanced groups, block randomization will be used. Pregnant women will be randomized in blocks of 6 with a total number of blocks to be 40. This will be conducted using STATA16 software, which will generate random permutations of sequential IDs of eligible study participants and their assignment to the treatment arms. This will be transferred to the REDCap in which a database will be created to facilitate random assignment during recruitment while maintaining concealment of randomization.
| Arm | Type | Receives |
|---|---|---|
| Erythromycin | Experimental | Drug: AntibioticsReceive 1) erythromycin 250 mg iv every 6 hours for 48 hours followed by 333 mg orally (pills) every 8 hours for 5 days |
| Azithromycin | Experimental | Drug: AntibioticsReceive azithromycin 500 mg iv daily for 48 hours followed by 500 mg orally (pills) for 5 days. |
Who may qualify
- Ages
- 18 to 50 years
- Sex
- Female only
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (3 listed)
- Singleton pregnancy
- PPROM from 22 weeks 0 days to 31 weeks 6 days at Sentara Norfolk General Hospital
- Membrane rupture within 36 hours of randomization, cervical dilation 3 cm or less, and 4 or fewer contractions in the 60-minutes monitoring before randomization
Key exclusion criteria (5 listed)
- Non-reassuring fetal heart tracing
- Vaginal bleeding
- Indications for delivery
- Received any antibiotic therapy within 7 days other than initiation of Ampicillin treatment as part of latency antibiotics prior to transfer to Sentara Norfolk General Hospital
- Allergy to penicillin, erythromycin, or azithromycin
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 |
|---|---|---|
| AntibioticsAlso: Latency antibiotics, Broad-spectrum antibioticsIn the absence of labor, broad-spectrum antibiotics (often called latency antibiotics) are recommended for women with PPROM less than 34 weeks to reduce chorioamnionitis, prolong latency, and decrease neonatal sepsis (12,13). | Drug | Azithromycin, Erythromycin |
Primary outcome
Latency Period
Time frame: At delivery
The time interval between the first antibiotic dose to time of delivery.
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Apr 2022.
- Background: PubMed 21508700Waters TP, Mercer B. Preterm PROM: prediction, prevention, principles. Clin Obstet Gynecol. 2011 Jun;54(2):307-12. doi: 10.1097/GRF.0b013e318217d4d3.
- Background: PubMed 3578431Meis PJ, Ernest JM, Moore ML. Causes of low birth weight births in public and private patients. Am J Obstet Gynecol. 1987 May;156(5):1165-8. doi: 10.1016/0002-9378(87)90133-5.
- Background: PubMed 3752169Beydoun SN, Yasin SY. Premature rupture of the membranes before 28 weeks: conservative management. Am J Obstet Gynecol. 1986 Sep;155(3):471-9. doi: 10.1016/0002-9378(86)90257-7.
- Background: PubMed 7070724Garite TJ, Freeman RK. Chorioamnionitis in the preterm gestation. Obstet Gynecol. 1982 May;59(5):539-45.
- Background: PubMed 32109463Pergialiotis V, Bellos I, Fanaki M, Antsaklis A, Loutradis D, Daskalakis G. The impact of residual oligohydramnios following preterm premature rupture of membranes on adverse pregnancy outcomes: a meta-analysis. Am J Obstet Gynecol. 2020 Jun;222(6):628-630. doi: 10.1016/j.ajog.2020.02.022. Epub 2020 Feb 25. No abstract available.
- Background: PubMed 23212881Costeloe KL, Hennessy EM, Haider S, Stacey F, Marlow N, Draper ES. Short term outcomes after extreme preterm birth in England: comparison of two birth cohorts in 1995 and 2006 (the EPICure studies). BMJ. 2012 Dec 4;345:e7976. doi: 10.1136/bmj.e7976.
- Background: PubMed 15635108Marlow N, Wolke D, Bracewell MA, Samara M; EPICure Study Group. Neurologic and developmental disability at six years of age after extremely preterm birth. N Engl J Med. 2005 Jan 6;352(1):9-19. doi: 10.1056/NEJMoa041367.
- Background: PubMed 7493703Averbuch B, Mazor M, Shoham-Vardi I, Chaim W, Vardi H, Horowitz S, Shuster M. Intra-uterine infection in women with preterm premature rupture of membranes: maternal and neonatal characteristics. Eur J Obstet Gynecol Reprod Biol. 1995 Sep;62(1):25-9. doi: 10.1016/0301-2115(95)02176-8.
- Background: PubMed 18667175Shen TT, DeFranco EA, Stamilio DM, Chang JJ, Muglia LJ. A population-based study of race-specific risk for preterm premature rupture of membranes. Am J Obstet Gynecol. 2008 Oct;199(4):373.e1-7. doi: 10.1016/j.ajog.2008.05.011. Epub 2008 Jul 29.
- Background: PubMed 27245741Drassinower D, Friedman AM, Obican SG, Levin H, Gyamfi-Bannerman C. Prolonged latency of preterm prelabour rupture of membranes and neurodevelopmental outcomes: a secondary analysis. BJOG. 2016 Sep;123(10):1629-35. doi: 10.1111/1471-0528.14133. Epub 2016 May 31.
- Background: PubMed 31405887Boghossian NS, Geraci M, Lorch SA, Phibbs CS, Edwards EM, Horbar JD. Racial and Ethnic Differences Over Time in Outcomes of Infants Born Less Than 30 Weeks' Gestation. Pediatrics. 2019 Sep;144(3):e20191106. doi: 10.1542/peds.2019-1106. Epub 2019 Aug 12.
- Background: PubMed 24297389Kenyon S, Boulvain M, Neilson JP. Antibiotics for preterm rupture of membranes. Cochrane Database Syst Rev. 2013 Dec 2;2013(12):CD001058. doi: 10.1002/14651858.CD001058.pub3.
- Individual participant dataSharing planned: No
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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.
Tetsuya Kawakita, MD principal investigator
Eastern Virginia Medical School
Questions about this trial
What is this clinical trial studying?
A study testing Antibiotics in people with Preterm Premature Rupture of Membrane, run by Eastern Virginia Medical School.
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 3 inclusion and 5 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: status not confirmed, as of the sponsor's last update on 14 Apr 2022. Status can change between updates, so confirm with the study contact before making plans.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Tetsuya Kawakita, MD (757-446-7900, kawakit@evms.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Latency Period (time frame: At delivery). 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 NCT05328817, which also lists 24 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 14 Apr 2022.