Selective Antibiotics When Symptoms Develop Versus Universal Antibiotics for Preterm Neonates (SAUNA)

Indian Council of Medical Research (ICMR)

Status and phase

Not yet enrolling

Phase 3

Conditions

Preterm Premature Rupture of Membrane

Early-Onset Neonatal Sepsis

PROM, Preterm (Pregnancy)

Preterm Birth

Sepsis

Treatments

Drug: Antibiotics

Study type

Interventional

Funder types

Other

Identifiers

NCT06377397

IIRPIG-2023-0000070

Details and patient eligibility

About

Preterm infants are born at less than 37 weeks of pregnancy. Sometimes a break or tear in the fluid filled bag that surrounds and protects the infant during pregnancy leads to an untimely birth. This state puts the infant at risk of serious condition called sepsis. Sepsis is a condition in which body responds inappropriately to an infection. Sepsis may progress to septic shock which can result in the loss of life. Doctors give antibiotics to treat sepsis.

The goal of this research study is to find out:

Among neonates at risk of early-onset neonatal sepsis, whether a policy of administering antibiotics selectively to a subset of at-risk infants who later develop signs of sepsis is not inferior to administering antibiotics to all at-risk infants in the 1st week of life.
To find out if infants receiving selective antibiotics (as above) compared to those receiving antibiotics from birth (as above) require fewer antibiotic courses of 48 hours duration or more in the 1st week of life.
To find out whether infants receiving selective antibiotics (as above) compared to those receiving antibiotics from birth (as above) are significantly different with respect to a wide range of secondary outcomes (listed under "Outcomes").

Full description

Sepsis is the major cause of neonatal mortality and early-onset neonatal sepsis (EONS) accounts for more than two-thirds of all cases of neonatal sepsis. Prolonged rupture of membranes (PROM) and preterm premature rupture of membranes (pPROM) are important risk factors of EONS. There is equipoise in the published literature whether antibiotics must be immediately initiated among all preterm neonates (<35 weeks gestation) delivered following PROM or pPROM who are asymptomatic at birth or whether antibiotics can be selectively administered if and when the at-risk neonates become symptomatic.

Among neonates <35 weeks gestation born with PROM >18 hours or pPROM and who are either asymptomatic or have no symptoms of sepsis at 4 hrs postnatally (P), is selectively administering antibiotics to neonates who later develop clinical sepsis [I] compared to administering antibiotics pre-emptively to all at-risk neonates [C] non-inferior with respect to the composite outcome of "mortality and/or culture-positive sepsis and/or severe sepsis" [O] within 7 days after enrolment [T] by an absolute margin of 7% [E] in a randomized controlled trial (S)? The trial will also have a superiority outcome: "need for antibiotic treatment lasting greater than 48 hours within 7 days after enrolment". The absolute superiority margin will be 50%.

The main objectives are as follows:

To determine whether antibiotics administered selectively to at-risk preterm neonates [<35 weeks gestation with prolonged rupture of membranes (PROM) or preterm premature rupture of membranes (pPROM)] when they develop signs of sepsis compared to administering antibiotics from birth to all at-risk neonates is non-inferior with respect to the primary outcome of "mortality or any episode of culture-positive sepsis or severe sepsis" in the 1st week of life
To determine whether neonates receiving selective antibiotics (as above) compared to those receiving antibiotics from birth (as above) are superior with respect to the co-primary outcome of fewer antibiotic courses of 48 hours duration or more in the 1st week of life
To determine whether neonates receiving selective antibiotics (as above) compared to those receiving antibiotics from birth (as above) are significantly different with respect to a wide range of secondary outcomes (listed under "Outcomes")

Enrollment

1,500 estimated patients

Sex

All

Ages

Under 4 hours old

Volunteers

No Healthy Volunteers

Inclusion and exclusion criteria

Inclusion criteria:

Gestational age of 26 to 34 weeks
Chronological age 4 hours
Have any one or both of the following risk factors of EONS:
- Prolonged rupture of membranes >18 hours
- Pre-labour rupture of membranes [as all subjects will be preterm, this is effectively pPROM]
Are either asymptomatic or have no signs attributable to sepsis at 4 hours. This will be defined as absence of the following clinical signs or need for interventions mentioned below:
1. Apnea (Standard definition) requiring intervention at any time until enrolment.
2. Need for a fluid bolus or inotropic support at any time until enrolment.
3. Seizures or seizure-like activity at any time until enrolment.
4. Upper GI bleed in the absence of a history of ante-partum hemorrhage at any time until enrolment.
5. Pus from any site at any time until enrolment.
6. Need for CPAP >6 cms of water with FiO2 >35% at 6-8 hours OR need for CPAP £6 cms and FiO2 £35% but with increasing requirement of support**
7. Chest Xray (if performed) with radiological features of pneumonia.
8. Need for intubation and mechanical ventilation.
9. Temperature >37.5°C or <36°C, unexplained by environmental causes
10. Feed intolerance [bilious or bloodstained vomiting (or gastric residuals) or visibly distended abdomen or >50% of the previous feed volume as gastric residuals]
11. Lethargy or unarousability
12. Sclerema
  
  Exclusion Criteria:
  
  Subjects will be excluded if they have any 1 of the following:

1. Life-threatening congenital malformation
2. Severe perinatal asphyxia (Apgar score <5 at 10 minutes or cord pH <7.0)
3. Clinical chorioamnionitis# [see definition below]
4. Foul-smelling liquor
5. Multiple gestation
6. Received a dose of antibiotics
7. Positive amniotic fluid culture (if performed and available prior to randomization)
8. Treating neonatologist unwilling to enroll the patient in the trial on the grounds that the patient needs antibiotics.