## Protocol Section
### Identification Module
**NCT ID:** NCT01401179

**Acronym:** PPROM

**Brief Title:** Antibiotics Study in Preterm Premature Rupture of the Membranes

**Official Title:** Randomized Phase III Trial of Cefazolin or Combination of Cefazolin and Erythromycin or Cefazolin and Clarithromycin in Women With Preterm Premature Rupture of the Membranes

#### Organization Study ID Info
**ID:** 2005-04-003
#### Organization
**Class:** OTHER
**Full Name:** Samsung Medical Center
### Status Module
#### Completion Date
**Date:** 2010-04

**Type:** ACTUAL

#### Expanded Access Info
#### Last Update Post Date
**Date:** 2011-08-08

**Type:** ESTIMATED

**Last Update Submit Date:** 2011-08-05

**Overall Status:** COMPLETED

#### Primary Completion Date
**Date:** 2010-04

**Type:** ACTUAL

#### Start Date
**Date:** 2005-04

**Status Verified Date:** 2011-07

#### Study First Post Date
**Date:** 2011-07-25
**Type:** ESTIMATED
**Study First Submit Date:** 2011-07-19
**Study First Submit QC Date:** 2011-07-22
### Sponsor Collaborators Module

#### Lead Sponsor

**Class:** OTHER

**Name:** Samsung Medical Center

#### Responsible Party

**Old Name Title:** Soo-young Oh, M.D. PhD

**Old Organization:** Department of Obstetrics and Gynecology, Samsung Medical Center, Sungkyunkwan University School of Medicine

### Oversight Module

**Oversight Has DMC:** True

### Description Module

**Brief Summary:** The purpose of this study is to compare the efficacy on maternal infection, chorioamnionitis and neonatal morbidity and mortality, and to review the evidence and provide recommendations on the use of antibiotics in PPROM.

**Detailed Description:** Despite major advances in perinatal care, preterm delivery is still the predominant cause of perinatal mortality and a major cause of neurological morbidity and mortality. Although the determinants of preterm labor and delivery are uncertain, evidence suggests intrauterine infection is a contributing factor. Antibiotic therapy for women in preterm premature rupture of membranes has been a routine practice. However the optimal regimen remains unclear and the choice of latency antibiotic regimen is at the discretion of admitting physician. The group 1 is treated only with cefazolin (1.0mg iv every 6 hours for 7 days). The group 2 is given a combination of cefazolin(1.0mg iv every 6 hours for 7 days) and erythromycin(250mg p.o. four times a day for 7 days). In group 3, clarithromycin (500mg p.o. 4 times a day for 7 days) was treated with cefazolin(1.0mg iv every 6 hours for 7 days). This study is designed to compare the efficacy on maternal infection, chorioamnionitis and neonatal morbidity and mortality and to review the evidence and provide recommendations on the use of antibiotics, especially by comparing the combination regimen in PPROM.

### Conditions Module

**Conditions:**

- Preterm Premature Rupture of the Membranes

**Keywords:**

- Preterm Premature Rupture of Fetal Membranes

- antibiotic therapy

### Design Module

#### Design Info

**Allocation:** RANDOMIZED

**Intervention Model:** FACTORIAL

##### Masking Info

**Masking:** SINGLE

**Who Masked:**

- OUTCOMES_ASSESSOR

**Primary Purpose:** TREATMENT

#### Enrollment Info

**Count:** 101

**Type:** ACTUAL

**Phases:**

- PHASE3

**Study Type:** INTERVENTIONAL

### Arms Interventions Module

#### Arm Group 1

**Intervention Names:**

- Drug: cefazolin, erythromycin, clarithromycin

**Label:** cefazolin

**Type:** ACTIVE_COMPARATOR

#### Arm Group 2

**Description:** cefazolin, erythromycin

**Intervention Names:**

- Drug: cefazolin, erythromycin, clarithromycin

**Label:** cefazolin plus erythromycin

**Type:** ACTIVE_COMPARATOR

#### Arm Group 3

**Intervention Names:**

- Drug: cefazolin, erythromycin, clarithromycin

**Label:** cefazolin plus clarithromycin

**Type:** ACTIVE_COMPARATOR

### Interventions

#### Intervention 1

**Arm Group Labels:**

- cefazolin

- cefazolin plus clarithromycin

- cefazolin plus erythromycin

**Description:** Antibiotics regimen was one of cefazolin or cefazolin plus erythromycin or cefazolin plus clarithromycin. Intravenous 1g cefazolin was given every 6 hours after negative result skin test for allergic reaction. With cefazolin plus erythromycin group or cefazolin plus clarithromycin, cefazolin was given with same protocol and 250mg oral erythromycin every 6 hours or 500mg oral clarithromycin every 12 hours was added. All antibiotics were given for 7 days or until delivery.

**Name:** cefazolin, erythromycin, clarithromycin

**Type:** DRUG

### Outcomes Module

#### Primary Outcomes

**Description:** 1. respiratory distress syndrome(RDS)
2. bronchopulmonary dysplasia(BPD)
3. intraventricular hemorrhage(IVH,≥grade 3)
4. retinopathy of prematurity(ROP,≥grade 3)
5. necrotizing enterocolitis(NEC,≥stage 2)
6. proven neonatal sepsis

**Measure:** Neonatal composite morbidity

**Time Frame:** Participants will be followed for duration of hospital day after delivery, an expected average of 8 weeks.

#### Secondary Outcomes

**Measure:** the incidence of abnormal brain sonography

**Time Frame:** Participants will be followed for duration of hospital day after delivery, an expected average of 8 weeks.

**Description:** The outcome was evaluated in five sub-domains (development, neurologic examination, Bayley Scales of Infant Development-II, vision, and hearing). The final outcome scale was divided into normal, mild, moderate, and severe disability.

**Measure:** infantile neurologic outcome

**Time Frame:** at 6 months and 1 year of corrected age

### Eligibility Module

**Eligibility Criteria:** Inclusion Criteria:

* PPROM, PA 23+0\~33+0wks
* ROM \<48 hrs before randomization
* singleton
* Cervical dilatation \<3cm
* uterine contraction less than 4 times per 1 hr

Exclusion Criteria:

* Major fetal malformation
* Multifetal pregnancy
* Rupture of the membrane \>8hrs before randomization
* Prior antibiotics use at local clinic before referral
* Vaginal bleeding
* IIOC (incompetent internal os of cervix)
* Placenta previa
* Gestational diabetes or overt diabetes
* Hypertensive disorders in pregnancy
* Liver cirrhosis
* Acute renal failure
* IUGR(Intrauterine growth restriction)

**Sex:** FEMALE

**Standard Ages:**

- CHILD

- ADULT

- OLDER_ADULT

### Contacts Locations Module

#### Locations

**Location 1:**

**City:** Seoul

**Country:** Korea, Republic of

**Facility:** Samsung Medical center

**Zip:** 135-710

#### Overall Officials

**Official 1:**

**Affiliation:** Samsung Medical Center

**Name:** Soo-Young Oh, M.D., PhD

**Role:** PRINCIPAL_INVESTIGATOR

## Derived Section

### Condition Browse Module - Ancestors

- ID: D000007752

- Term: Obstetric Labor, Premature

- ID: D000007744

- Term: Obstetric Labor Complications

- ID: D000011248

- Term: Pregnancy Complications

- ID: D000005261

- Term: Female Urogenital Diseases and Pregnancy Complications

- ID: D000091642

- Term: Urogenital Diseases

- ID: D000014947

- Term: Wounds and Injuries

### Condition Browse Module - Browse Branches

- Abbrev: BXS

- Name: Urinary Tract, Sexual Organs, and Pregnancy Conditions

- Abbrev: All

- Name: All Conditions

- Abbrev: BC26

- Name: Wounds and Injuries

### Condition Browse Module - Browse Leaves

- ID: M25869

- Name: Premature Birth

- Relevance: HIGH

- As Found: Premature

- ID: M15241

- Name: Rupture

- Relevance: HIGH

- As Found: Rupture

- ID: M8452

- Name: Fetal Membranes, Premature Rupture

- Relevance: HIGH

- As Found: Preterm Premature Rupture of the Membranes

- ID: M10772

- Name: Obstetric Labor, Premature

- Relevance: LOW

- As Found: Unknown

- ID: M10764

- Name: Obstetric Labor Complications

- Relevance: LOW

- As Found: Unknown

- ID: M14127

- Name: Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M2875

- Name: Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M27093

- Name: Female Urogenital Diseases

- Relevance: LOW

- As Found: Unknown

- ID: M8399

- Name: Female Urogenital Diseases and Pregnancy Complications

- Relevance: LOW

- As Found: Unknown

- ID: M17685

- Name: Wounds and Injuries

- Relevance: LOW

- As Found: Unknown

### Condition Browse Module - Meshes

- ID: D000047928

- Term: Premature Birth

- ID: D000005322

- Term: Fetal Membranes, Premature Rupture

- ID: D000012421

- Term: Rupture

### Intervention Browse Module - Ancestors

- ID: D000000900

- Term: Anti-Bacterial Agents

- ID: D000000890

- Term: Anti-Infective Agents

- ID: D000011500

- Term: Protein Synthesis Inhibitors

- ID: D000004791

- Term: Enzyme Inhibitors

- ID: D000045504

- Term: Molecular Mechanisms of Pharmacological Action

- ID: D000065692

- Term: Cytochrome P-450 CYP3A Inhibitors

- ID: D000065607

- Term: Cytochrome P-450 Enzyme Inhibitors

- ID: D000005765

- Term: Gastrointestinal Agents

### Intervention Browse Module - Browse Branches

- Abbrev: Infe

- Name: Anti-Infective Agents

- Abbrev: All

- Name: All Drugs and Chemicals

- Abbrev: Gast

- Name: Gastrointestinal Agents

### Intervention Browse Module - Browse Leaves

- ID: M5687

- Name: Cefazolin

- Relevance: HIGH

- As Found: EUS-

- ID: M4222

- Name: Anti-Bacterial Agents

- Relevance: LOW

- As Found: Unknown

- ID: M4224

- Name: Antibiotics, Antitubercular

- Relevance: LOW

- As Found: Unknown

- ID: M19585

- Name: Clarithromycin

- Relevance: HIGH

- As Found: Prescription

- ID: M8068

- Name: Erythromycin

- Relevance: HIGH

- As Found: 1 or 2

- ID: M8069

- Name: Erythromycin Estolate

- Relevance: HIGH

- As Found: 1 or 2

- ID: M18236

- Name: Erythromycin Ethylsuccinate

- Relevance: HIGH

- As Found: 1 or 2

- ID: M195803

- Name: Erythromycin stearate

- Relevance: HIGH

- As Found: 1 or 2

- ID: M4214

- Name: Anti-Infective Agents

- Relevance: LOW

- As Found: Unknown

- ID: M7951

- Name: Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M30564

- Name: Cytochrome P-450 CYP3A Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M30537

- Name: Cytochrome P-450 Enzyme Inhibitors

- Relevance: LOW

- As Found: Unknown

- ID: M8881

- Name: Gastrointestinal Agents

- Relevance: LOW

- As Found: Unknown

### Intervention Browse Module - Meshes

- ID: D000017291

- Term: Clarithromycin

- ID: D000002437

- Term: Cefazolin

- ID: D000004917

- Term: Erythromycin

- ID: D000004918

- Term: Erythromycin Estolate

- ID: D000015643

- Term: Erythromycin Ethylsuccinate

- ID: C000011462

- Term: Erythromycin stearate

### Misc Info Module

- Version Holder: 2024-05-24
