Trial Outcomes & Findings for Study of Effectiveness and Safety of Azithromycin-based Extended-spectrum Prophylaxis to Prevent Post Cesarean Infection (NCT NCT01235546)

NCT ID: NCT01235546

Last Updated: 2017-07-28

Results Overview

Endometritis was defined as the presence of at least two of the following signs with no other recognized cause: fever (temperature of at least 38°C \[100.4°F\]), abdominal pain, uterine tenderness, or purulent drainage from the uterus. Wound infection was defined as the presence of either superficial or deep incisional surgical-site infection characterized by cellulitis or erythema and induration around the incision or purulent discharge from the incision site with or without fever and included necrotizing fasciitis. Wound hematoma, seroma, or breakdown alone in the absence of the preceding signs did not constitute infection.

• Recruitment status: COMPLETED
• Study phase: NA
• Target enrollment: 2013 participants
• Primary outcome timeframe: Up to 6 weeks after delivery
• Results posted on: 2017-07-28

Participant Flow

Patients were randomly assigned to receive either azithromycin (at a dose of 500mg in 250 ml of saline, one time dose) or an identical-appearing saline placebo and the standard of care (cephazolin or clindamycin)

The addition of azithromycin and the standard of care (cephazolin or clindamycin) for antibiotic prophylaxis before cesarean delivery may further reduce the rate of postoperative infection. We evaluated the benefits and safety of azithromycin prophylaxis and the standard of care in women undergoing nonelective cesarean section.

Participant milestones

Measure	Placebo and Standard of Care Placebo: 250 cc normal saline Standard of care (cephazolin or clindamycin)	Azithromycin and Standard of Care Azithromycin: 500 mg in 250 cc normal saline 1 time dose and standard of care (cephazolin or clindamycin)
Overall Study STARTED	994	1019
Overall Study COMPLETED	992	1018
Overall Study NOT COMPLETED	2	1

Reasons for withdrawal

Measure	Placebo and Standard of Care Placebo: 250 cc normal saline Standard of care (cephazolin or clindamycin)	Azithromycin and Standard of Care Azithromycin: 500 mg in 250 cc normal saline 1 time dose and standard of care (cephazolin or clindamycin)
Overall Study Staff error, medication not administered	1	0
Overall Study Protocol Violation	1	1

Baseline Characteristics

Study of Effectiveness and Safety of Azithromycin-based Extended-spectrum Prophylaxis to Prevent Post Cesarean Infection

Baseline characteristics by cohort

Measure	Placebo With Standard Prophylaxis n=994 Participants Placebo: 250 cc normal saline Standard Prophylaxis: standard cephalosporin prophylaxis	Azithromycin (Zithromax) With Standard Prophylaxis n=1019 Participants Azithromycin: 500 mg in 250 cc normal saline 1 time dose Standard Prophylaxis: standard cephalosporin prophylaxis	Total n=2013 Participants Total of all reporting groups
Age, Continuous	28.4 years STANDARD_DEVIATION 6.5 • n=5 Participants	28.2 years STANDARD_DEVIATION 6.1 • n=7 Participants	28.3 years STANDARD_DEVIATION 6.3 • n=5 Participants
Sex: Female, Male Female	994 Participants n=5 Participants	1019 Participants n=7 Participants	2013 Participants n=5 Participants
Sex: Female, Male Male	0 Participants n=5 Participants	0 Participants n=7 Participants	0 Participants n=5 Participants
Region of Enrollment United States	994 participants n=5 Participants	1019 participants n=7 Participants	2013 participants n=5 Participants
Smoking Prevalence	122 Participants n=5 Participants	97 Participants n=7 Participants	219 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 6 weeks after delivery

Population: The specific characteristics related to the cesarean delivery, including indications for cesarean delivery, receipt of standard prophylaxis, timing of receipt of study medication, and type of surgical skin preparation, were similar in the two groups.

Endometritis was defined as the presence of at least two of the following signs with no other recognized cause: fever (temperature of at least 38°C [100.4°F]), abdominal pain, uterine tenderness, or purulent drainage from the uterus. Wound infection was defined as the presence of either superficial or deep incisional surgical-site infection characterized by cellulitis or erythema and induration around the incision or purulent discharge from the incision site with or without fever and included necrotizing fasciitis. Wound hematoma, seroma, or breakdown alone in the absence of the preceding signs did not constitute infection.

Outcome measures

Measure	Placebo n=992 Participants 250 cc normal saline Placebo: 250 cc normal saline	Azithromycin n=1018 Participants Azithromycin: 500 mg in 250 cc normal saline 1 time dose
Participants With Endometritis and/or Wound Infection and/or Other Post-cesarean Infections (Occurring Within 6 Weeks of Delivery)	119 Participants	62 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 months after birth

morbidities include: death, Respiratory Distress Syndrome (RDS), Bronchopulmonary Dysplasia (BPD), Periventricular Leukomalacia (PVL) suspected or proven sepsis, Necrotizing Enterocolitis (NEC) Intraventricular Hemorrhage (IVH) and systemic inflammatory response syndrome

Outcome measures

Measure	Placebo n=992 Participants 250 cc normal saline Placebo: 250 cc normal saline	Azithromycin n=1018 Participants Azithromycin: 500 mg in 250 cc normal saline 1 time dose
Neonatal Morbidities (Listed Below)	135 Participants	146 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 months after birth

Neonates who are admitted to the NICU due to morbidities diagnosed from birth and up to three months of life. Morbidities as defined in the Neonatal morbidities outcome measure.

Outcome measures

Measure	Placebo n=992 Participants 250 cc normal saline Placebo: 250 cc normal saline	Azithromycin n=1018 Participants Azithromycin: 500 mg in 250 cc normal saline 1 time dose
Neonatal Intensive Care Unit (NICU) Admission	169 Participants	171 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 months after birth

Population: Hospitalization after discharge

Outcome measures

Measure	Placebo n=992 Participants 250 cc normal saline Placebo: 250 cc normal saline	Azithromycin n=1018 Participants Azithromycin: 500 mg in 250 cc normal saline 1 time dose
Neonatal Readmission	43 Participants	39 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 6 weeks after delivery

Population: Postpartum Fever

Outcome measures

Measure	Placebo n=992 Participants 250 cc normal saline Placebo: 250 cc normal saline	Azithromycin n=1018 Participants Azithromycin: 500 mg in 250 cc normal saline 1 time dose
Maternal Fever	81 Participants	51 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 6 weeks after delivery

Maternal postpartum unscheduled visit or readmission to the hospital

Outcome measures

Measure	Placebo n=992 Participants 250 cc normal saline Placebo: 250 cc normal saline	Azithromycin n=1018 Participants Azithromycin: 500 mg in 250 cc normal saline 1 time dose
Maternal Postpartum Readmission or Unscheduled Visit	123 Participants	83 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 6 weeks after delivery

Maternal postpartum use of antibiotics

Outcome measures

Measure	Placebo n=992 Participants 250 cc normal saline Placebo: 250 cc normal saline	Azithromycin n=1018 Participants Azithromycin: 500 mg in 250 cc normal saline 1 time dose
Maternal Postpartum Antibiotic Use	166 Participants	126 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 6 weeks after delivery

All maternal serious adverse events

Outcome measures

Measure	Placebo n=992 Participants 250 cc normal saline Placebo: 250 cc normal saline	Azithromycin n=1018 Participants Azithromycin: 500 mg in 250 cc normal saline 1 time dose
Maternal Serious Adverse Events	29 Participants	15 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: Up to 3 months after birth

Composite for all neonatal serious adverse events

Outcome measures

Measure	Placebo n=992 Participants 250 cc normal saline Placebo: 250 cc normal saline	Azithromycin n=1018 Participants Azithromycin: 500 mg in 250 cc normal saline 1 time dose
Neonatal Serious Adverse Events	5 Participants	7 Participants

OTHER_PRE_SPECIFIED outcome

Timeframe: up to 3 months after birth

Any diagnosis of pyloric stenosis based on clinical presentation and radiological and/or surgical confirmation

Outcome measures

Measure	Placebo n=992 Participants 250 cc normal saline Placebo: 250 cc normal saline	Azithromycin n=1018 Participants Azithromycin: 500 mg in 250 cc normal saline 1 time dose
Infant Pyloric Stenosis	1 Participants	2 Participants

Adverse Events

Placebo and Standard of Care

Serious events: 29 serious events

Other events: 14 other events

Deaths: 0 deaths

Azithromycin and Standard of Care

Serious events: 15 serious events

Other events: 9 other events

Deaths: 0 deaths

Serious adverse events

Measure	Placebo and Standard of Care n=992 participants at risk Placebo: 250 cc normal saline and Standard of care (cefazolin or clindamycin)	Azithromycin and Standard of Care n=1018 participants at risk Azithromycin: 500 mg in 250 cc normal saline and Standard of care (cefazolin or clindamycin)
Immune system disorders Severe allergic reaction	2.9% 29/992 • Number of events 29 • Up to 6 weeks after delivery Maternal serious adverse events (maternal safety composite outcome) included death, suspected allergic reactions (including anaphylaxis or generalized skin rash), any serious adverse event leading to the discontinuation of a study medication or suspected to be due to the medication, and any other reported serious adverse complication, including pulmonary embolism, admission to an intensive care unit (ICU), and cardiac events.	1.5% 15/1018 • Number of events 15 • Up to 6 weeks after delivery Maternal serious adverse events (maternal safety composite outcome) included death, suspected allergic reactions (including anaphylaxis or generalized skin rash), any serious adverse event leading to the discontinuation of a study medication or suspected to be due to the medication, and any other reported serious adverse complication, including pulmonary embolism, admission to an intensive care unit (ICU), and cardiac events.

Other adverse events

Measure	Placebo and Standard of Care n=992 participants at risk Placebo: 250 cc normal saline and Standard of care (cefazolin or clindamycin)	Azithromycin and Standard of Care n=1018 participants at risk Azithromycin: 500 mg in 250 cc normal saline and Standard of care (cefazolin or clindamycin)
General disorders ICU admission	1.4% 14/992 • Number of events 14 • Up to 6 weeks after delivery Maternal serious adverse events (maternal safety composite outcome) included death, suspected allergic reactions (including anaphylaxis or generalized skin rash), any serious adverse event leading to the discontinuation of a study medication or suspected to be due to the medication, and any other reported serious adverse complication, including pulmonary embolism, admission to an intensive care unit (ICU), and cardiac events.	0.88% 9/1018 • Number of events 9 • Up to 6 weeks after delivery Maternal serious adverse events (maternal safety composite outcome) included death, suspected allergic reactions (including anaphylaxis or generalized skin rash), any serious adverse event leading to the discontinuation of a study medication or suspected to be due to the medication, and any other reported serious adverse complication, including pulmonary embolism, admission to an intensive care unit (ICU), and cardiac events.

Additional Information

Alan Tita, MD

University of Alabama at Birmingham, Maternal & Fetal Medicine

Phone: 205-934-9616

Email: atita@uab.edu

Results disclosure agreements

• Principal investigator is a sponsor employee
• Publication restrictions are in place