Preterm Premature Rupture of MembranePhase 4NCT06396078
Improvement of PPROM Management With Prophylactic Antimicrobial Therapy (iPROMPT)
A Phase 4 study testing Ceftriaxone 1000 MG, Clarithromycin 500mg and Metronidazole 500 mg in people with Preterm Premature Rupture of Membrane and Pregnancy, High Risk, run by Ohio State University at 2 sites in United States.
Trial summary
To conduct an unblinded pragmatic randomized controlled trial (pRCT) "Improvement of PPROM Management with Prophylactic Antimicrobial Therapy (iPROMPT)" of a seven-day course of ceftriaxone, clarithromycin, and metronidazole versus the current standard of care of a seven-day course of ampicillin/amoxicillin and… Read more about this study
- Who is it for?
- Ages 18 years and older, women only
- Conditions the study is for
- Preterm Premature Rupture of Membrane, Pregnancy, High Risk, Preterm Birth
- What is being tested?
- Ceftriaxone 1000 MG, Clarithromycin 500mg and Metronidazole 500 mg
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 56 participants
- Where
- 2 sitesUnited States
- Study dates
- 18 Jul 2024to Dec 2026
- Phase
- Phase 4
- Are there results?
- Not yet: the study is under way
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
- Admitted to the inpatient unit for expectant management of PPROM until delivery
- Age ≥ 18 years with the ability to provide informed consent
- Gestational age between 23 0/7 and 32 6/7 weeks
Who cannot join
- Having received more than one dose of any prophylactic antibiotic
- Suspected or confirmed infection requiring treatment with antibiotics
- Allergy or contraindication to an antibiotic in either arm
- Maternal immunosuppression
Trial locations and contacts
2 sites in 1 country. Contact the study team or a site near you to ask about taking part.
United States2 sites, 2 recruiting
- Recruiting
The Ohio State University Wexner Medical Center OB/GYN Maternal and Fetal Medicine
Columbus, Ohio, 43210
Marissa Berry, MD, 614-293-4780, Marissa.Berry@osumc.edu
- Recruiting
University of Texas Medical Branch
Galveston, Texas, 775555
Benjamin Spires, MD, 409-772-1193, bpspires@UTMB.EDU
Luis D Pacheco, MD, ldpachec@utmb.edu
About this study
Official title: Improvement of PPROM Management With Prophylactic Antimicrobial Therapy
To conduct an unblinded pragmatic randomized controlled trial (pRCT) "Improvement of PPROM Management with Prophylactic Antimicrobial Therapy (iPROMPT)" of a seven-day course of ceftriaxone, clarithromycin, and metronidazole versus the current standard of care of a seven-day course of ampicillin/amoxicillin and azithromycin or erythromycin to prolong pregnancy and decrease adverse perinatal outcomes among hospitalized pregnant individuals undergoing expectant management of PPROM <34 weeks.
Read the detailed description
Preterm prelabor rupture of membranes (PPROM) is the most common identifiable risk factor associated with preterm birth and affects 1 in 3 pregnant individuals in the United States with spontaneous preterm birth. Individuals diagnosed with PPROM who meet criteria for expectant management are currently admitted to the hospital for observation until delivery, which is generally recommended at 34 weeks' gestation unless indicated sooner. Initially upon admission, a course of prophylactic antibiotics is administered as this has been shown to prolong pregnancy and improve neonatal outcomes. The standard antibiotic regimen, primarily based on data published in 1997, includes ampicillin followed by amoxicillin with erythromycin or azithromycin for a total of 7 days. Ongoing studies are needed to determine the optimal prophylactic antibiotic regimen given changes in bacterial sensitivities over time, lack of adequate coverage for common organisms including genital mycoplasma, inadequate placental transfer of currently used antibiotic agents, ineffective antibiotic response at reducing the fetal inflammatory response, and new promising antibiotic agents that address these limitations. A promising expanded-spectrum alternative regimen with proof-of-concept is ceftriaxone, clarithromycin, and metronidazole. Observational studies have shown successful eradication of intraamniotic inflammation/infection using this new regimen. This regimen offers multiple potential advantages, including: higher bioavailability, higher transplacental transfer, and effectiveness against genital mycoplasma (clarithromycin), greater anaerobic coverage (metronidazole), and a longer half-life and expanded coverage against gram-negative bacteria (ceftriaxone) compared with the current standard regimen.
- Being tested
- Ceftriaxone 1000 MG, Clarithromycin 500mg, Metronidazole 500 mg, Ampicillin 2 GM Injection, Amoxicillin 250 MG
- Keywords
- Pregnancy, Preterm premature rupture of membranes, Latency, Chorioamnionitis, Antibiotic prophylaxis
- Medical subject headings
- Preterm Premature Rupture of the Membranes, Premature Birth, Chorioamnionitis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Ceftriaxone 1000 MGDrug
Ceftriaxone 1 g IV q 24 hours x 7 days (in addition to clarithromycin and metronidazole)
Clarithromycin 500mgDrug
Clarithromycin 500 mg PO BID x 7 days (in addition to ceftriaxone and metronidazole)
Metronidazole 500 mgDrug
Metronidazole 500 mg PO q 12 hours x 7 days (in addition to clarithromycin and ceftriaxone)
Ampicillin 2 GM InjectionDrug
Ampicillin 2 g IV q 6 hours x 48 hours (prior to amoxicillin and in addition to either azithromycin or erythromycin)
Amoxicillin 250 MGDrug
Amoxicillin 250 mg q 8 hours for an additional 5 days (following ampicillin and in addition to either azithromycin or erythromycin)
AzithromycinDrug
Azithromycin 1 g PO x 1 dose (in addition to ampicillin and amoxicillin)
ErythromycinDrug
Erythromycin 250 mg IV q 6 hours x 48 hours followed by erythromycin 333 mg PO TID for an additional 5 days (in addition to ampicillin and amoxicillin)
| Study group | Role | What they receive |
|---|---|---|
| Intervention group | Experimental | Participants randomized to the intervention group will receive the following regimen:
* Ceftriaxone 1 g IV q 24 hours x 7 days
* Clarithromycin 500 mg PO BID x 7 days
* Metronidazole 500 mg PO q 12 hours x 7 days Receives: Drug: Ceftriaxone 1000 MG; Drug: Clarithromycin 500mg; Drug: Metronidazole 500 mg |
| Standard of care | Other | Participants randomized to the standard care group will receive the following regimen:
* Ampicillin 2 g IV q 6 hours x 48 hours followed by amoxicillin 250 mg q 8 hours for an additional 5 days
* Azithromycin 1 g PO x 1 dose OR erythromycin 250 mg IV q 6 hours x 48 hours followed by erythromycin 333 mg PO TID for an additional 5 days Receives: Drug: Ampicillin 2 GM Injection; Drug: Amoxicillin 250 MG; Drug: Azithromycin; Drug: Erythromycin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Latency
Latency will be measured in hours, and also reported as days for clinical interpretability.
Measured: From randomization to delivery
Secondary outcomes (8)
Neonatal outcome composite checklist
Includes neonatal sepsis, respiratory distress syndrome, any mechanical ventilation, bronchopulmonary dysplasia, intraventricular hemorrhage, periventricular leukomalacia, necrotizing enterocolitis, stillbirth, or neonatal death
Measured: From birth to up to 6 weeks postpartum
Endometritis
Diagnosed If the patient develops two of the following 1) oral body temperature ≥101°F at any time, or a temperature of ≥100.4 °F 24 hours after delivery, 2) maternal tachycardia that parallels the temperature, 3) uterine tenderness, 4) purulent vaginal discharge, or 5) associated findings with advanced endometritis (dynamic ileus, pelvic peritonitis, pelvic abscess, bowel obstruction, necrosis of the lower uterine segment)
Measured: From birth to up to 6 weeks postpartum
Surgical site infection
Presence of either superficial or deep incisional SSI described as cellulitis/erythema and induration around the incision or purulent discharge from the incision site, with or without fever, such as necrotizing fasciitis (diagnosed based on necrotizing wound infection). Intraabdominal abscess may or may not be present. Wound hematoma, seroma, or incisional breakdown alone in the absence of the above signs does not constitute infection.
Measured: From birth to up to 6 weeks postpartum
Individual clinical infections
Measured: From birth to up to 6 weeks postpartum
Puerperal fever
temperature ≥ 100.4 °F at least twice 30 minutes apart, or once with the use of antipyretic, or ≥ 101 °F once. This will be analyzed for intrapartum and postpartum fever.
Measured: From birth to up to 6 weeks postpartum
Histopathologic chorioamnionitis/funisitis on histologic placental evaluation
Measured: From randomization to delivery
Antibiotic receipt postpartum
Measured: From birth to up to 6 weeks postpartum
Adverse events
Allergic reactions (anaphylaxis, angioedema, urticaria), Stevens Johnsons syndrome, gastrointestinal side effects (nausea, vomiting, constipation, diarrhea, ileus)
Measured: From randomization to delivery
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted2 May 2024
- Study start18 Jul 2024
- Primary completionDec 2026 (estimated)
- Study completionDec 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Preterm Premature Rupture of MembraneStudies 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 56 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Ohio State University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Kartik K Venkatesh, Ohio State University
- Investigators
- Marissa Berry, MD, Principal investigator, Ohio State UniversityKartik K Venkatesh, MD, PhD, Principal investigator, Ohio State University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06396078
- Sponsor's protocol ID
- 2024H0122
- Status last verified
- Jan 2026
- First submitted
- 25 Apr 2024
- Last updated
- 27 Jan 2026
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 27 Jan 2026. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Improvement of PPROM Management With Prophylactic Antimicrobial Therapy
- ClinicalTrials.gov ID
- NCT06396078
- Acronym / sponsor ID
- 2024H0122
- Keywords
- Pregnancy, Preterm premature rupture of membranes, Latency, Chorioamnionitis, Antibiotic prophylaxis
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Recruiting
- Enrolment
- 56 participants (estimated)
- Lead sponsor
- Ohio State UniversityUniversity, hospital or other
- Study start
- 18 Jul 2024 (actual)
- Primary completion
- Dec 2026 (estimated)
- Study completion
- Dec 2026 (estimated)
- First posted
- 2 May 2024 (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.
To conduct an unblinded pragmatic randomized controlled trial (pRCT) "Improvement of PPROM Management with Prophylactic Antimicrobial Therapy (iPROMPT)" of a seven-day course of ceftriaxone, clarithromycin, and metronidazole versus the current standard of care of a seven-day course of ampicillin/amoxicillin and azithromycin or erythromycin to prolong pregnancy and decrease adverse perinatal outcomes among hospitalized pregnant individuals undergoing expectant management of PPROM <34 weeks.
Detailed description
Preterm prelabor rupture of membranes (PPROM) is the most common identifiable risk factor associated with preterm birth and affects 1 in 3 pregnant individuals in the United States with spontaneous preterm birth. Individuals diagnosed with PPROM who meet criteria for expectant management are currently admitted to the hospital for observation until delivery, which is generally recommended at 34 weeks' gestation unless indicated sooner. Initially upon admission, a course of prophylactic antibiotics is administered as this has been shown to prolong pregnancy and improve neonatal outcomes. The standard antibiotic regimen, primarily based on data published in 1997, includes ampicillin followed by amoxicillin with erythromycin or azithromycin for a total of 7 days. Ongoing studies are needed to determine the optimal prophylactic antibiotic regimen given changes in bacterial sensitivities over time, lack of adequate coverage for common organisms including genital mycoplasma, inadequate placental transfer of currently used antibiotic agents, ineffective antibiotic response at reducing the fetal inflammatory response, and new promising antibiotic agents that address these limitations. A promising expanded-spectrum alternative regimen with proof-of-concept is ceftriaxone, clarithromycin, and metronidazole. Observational studies have shown successful eradication of intraamniotic inflammation/infection using this new regimen. This regimen offers multiple potential advantages, including: higher bioavailability, higher transplacental transfer, and effectiveness against genital mycoplasma (clarithromycin), greater anaerobic coverage (metronidazole), and a longer half-life and expanded coverage against gram-negative bacteria (ceftriaxone) compared with the current standard regimen.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intervention group | Experimental | Drug: Ceftriaxone 1000 MG, Drug: Clarithromycin 500mg, Drug: Metronidazole 500 mgParticipants randomized to the intervention group will receive the following regimen: * Ceftriaxone 1 g IV q 24 hours x 7 days * Clarithromycin 500 mg PO BID x 7 days * Metronidazole 500 mg PO q 12 hours x 7 days |
| Standard of care | Other | Drug: Ampicillin 2 GM Injection, Drug: Amoxicillin 250 MG, Drug: Azithromycin, Drug: ErythromycinParticipants randomized to the standard care group will receive the following regimen: * Ampicillin 2 g IV q 6 hours x 48 hours followed by amoxicillin 250 mg q 8 hours for an additional 5 days * Azithromycin 1 g PO x 1 dose OR erythromycin 250 mg IV q 6 hours x 48 hours followed by erythromycin 333 mg PO TID for an additional 5 days |
Who may qualify
- Ages
- 18 years and older
- Sex
- Female only
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (3 listed)
- Admitted to the inpatient unit for expectant management of PPROM until delivery
- Age ≥ 18 years with the ability to provide informed consent
- Gestational age between 23 0/7 and 32 6/7 weeks
Key exclusion criteria (4 listed)
- Having received more than one dose of any prophylactic antibiotic
- Suspected or confirmed infection requiring treatment with antibiotics
- Allergy or contraindication to an antibiotic in either arm
- Maternal immunosuppression
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 |
|---|---|---|
| Ceftriaxone 1000 MGCeftriaxone 1 g IV q 24 hours x 7 days (in addition to clarithromycin and metronidazole) | Drug | Intervention group |
| Clarithromycin 500mgClarithromycin 500 mg PO BID x 7 days (in addition to ceftriaxone and metronidazole) | Drug | Intervention group |
| Metronidazole 500 mgMetronidazole 500 mg PO q 12 hours x 7 days (in addition to clarithromycin and ceftriaxone) | Drug | Intervention group |
| Ampicillin 2 GM InjectionAmpicillin 2 g IV q 6 hours x 48 hours (prior to amoxicillin and in addition to either azithromycin or erythromycin) | Drug | Standard of care |
| Amoxicillin 250 MGAmoxicillin 250 mg q 8 hours for an additional 5 days (following ampicillin and in addition to either azithromycin or erythromycin) | Drug | Standard of care |
| AzithromycinAzithromycin 1 g PO x 1 dose (in addition to ampicillin and amoxicillin) | Drug | Standard of care |
| ErythromycinErythromycin 250 mg IV q 6 hours x 48 hours followed by erythromycin 333 mg PO TID for an additional 5 days (in addition to ampicillin and amoxicillin) | Drug | Standard of care |
Primary outcome
Latency
Time frame: From randomization to delivery
Latency will be measured in hours, and also reported as days for clinical interpretability.
8 secondary outcomes
Neonatal outcome composite checklist
Time frame: From birth to up to 6 weeks postpartum
Endometritis
Time frame: From birth to up to 6 weeks postpartum
Surgical site infection
Time frame: From birth to up to 6 weeks postpartum
Individual clinical infections
Time frame: From birth to up to 6 weeks postpartum
Puerperal fever
Time frame: From birth to up to 6 weeks postpartum
Histopathologic chorioamnionitis/funisitis on histologic placental evaluation
Time frame: From randomization to delivery
Antibiotic receipt postpartum
Time frame: From birth to up to 6 weeks postpartum
Adverse events
Time frame: From randomization to delivery
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 27 Jan 2026.
- 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.
Marissa Berry, MD principal investigator
Ohio State University
Kartik K Venkatesh, MD, PhD 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 4 study testing Ceftriaxone 1000 MG, Clarithromycin 500mg and Metronidazole 500 mg in people with Preterm Premature Rupture of Membrane and Pregnancy, High Risk, 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 3 inclusion and 4 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: looking for participants now, as of the sponsor's last update on 27 Jan 2026. 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. 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?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Marissa Berry, MD (614-293-4780, Marissa.Berry@osumc.edu), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Latency (time frame: From randomization to delivery). 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 27 Jan 2026.