India, with one of the world’s largest populations, continues to struggle with extremely high infant and neonatal mortality rates. Neonatal infection (sepsis) now accounts for 50 percent of deaths among community-born (and 20 percent of mortality among hospital-born) infants. This study is the first phase of a multi-phase project investigating interventions to prevent neonatal infection in India.

Condition	Phase
Sepsis	Phase I

Further Study Details: 

Expected Total Enrollment:  1000

Invasive bacterial infections encompass clinical diagnoses of septicemia, pneumonia, and meningitis. Together, these infections are termed “neonatal sepsis” and account for over half of the newborn deaths at the district and sub-district level in India. Sepsis is the most common (80-90 percent) primary diagnosis for admission in Indian hospitals. Phase 1 of this study is a prospective, epidemiologic study involving 1,000 community-based and hospital populations of newborn infants. It includes identifying all infants born in study hospitals and those brought to the hospitals with suspected sepsis; obtaining blood cultures from these infants and identifying the sepsis-causing bacteria; screening of all bacterial strains isolated from blood cultures for antimicrobial resistance; collecting basic demographic, risk factor, and treatment data on each case; and developing a computer-based system/network for data management. A village-level surveillance system was put in place to identify women during their pregnancy; monitor pregnancy outcomes; and establish a mechanism for referral of all potentially septic infants to participating clinics or hospitals for evaluation, including the collection of blood cultures. Potential sources of bacteria causing sepsis will be identified using molecular epidemiologic techniques. This involves matching blood isolates from septic infants born with colonizing isolates, that are obtained by screening skin, throat, and stool cultures from these infants and skin and vaginal cultures from their mothers.

Phase II will be a hospital based intervention (n = 396 infants) measuring the colonizing ability, safety, and tolerance of a probiotic supplement, Lactobacillus plantarum in the neonatal gut. Newborn infants ≥ 35 weeks of gestation will be randomized to receive either L. plantarum preparations (containing 109 organisms) or placebo preparations orally once a day for the first 7 days of life. The final stage of the project will be a community-based randomized double-blind placebo-controlled trial of L. plantarum enrolling over 8,000 newborns to examine the efficacy of probiotic supplementation in reducing neonatal infection in Indian neonates.

The sample size calculations assume a 20 to 30% culture-positivity rate and the use of approximately 200 positive blood culture isolates.

Ages Eligible for Study:  up to  60 Days,  Genders Eligible for Study:  Both

Accepts Healthy Volunteers

Criteria

Inclusion Criteria:

• Age <60 days
• A diagnosis of suspected sepsis/pneumonia, based on the presence of at least one of the following symptoms at admission: poor feeding/poor sucking, decreased activity/lethargy, fever, hypothermia, cyanosis, diarrhea, abdominal distension, seizures, apneic spells, sclerema, bleeding, jaundice, tachypnea, chest wall retractions, shock.
• Born in one of the participating hospitals or in village inside catchment area

If the screening physician does not suspect sepsis, even in the presence of one or more of the above signs, the baby should not be enrolled.

Exclusion Criteria:

• The presence of major congenital anomalies excludes admission to the study.

A major congenital anomaly is defined as any malformation that is felt to be life-threatening or that requires surgical intervention. If the medical officer is uncertain whether an anomaly is life-threatening, he/she should not enroll the infant.

Linda Wright, M.D.       wrightl@exchange.nih.gov

India
      Nair Hospital –TN Medical College, Mumbai,  India; Recruiting
India, Orissa
      Capital Hospital, Bhubaneswar,  Orissa,  India; Recruiting
      Ispat General Hospital, Rourkela,  Orissa,  India; Recruiting
      Kalinga Hospital, Bhubaneswar,  Orissa,  India; Recruiting

Study chairs or principal investigators

Pianki Panigrahi, M.D. Ph.D.,  Principal Investigator,  University of Maryland School of Medicine   

Study ID Numbers:  GN 07; U01 HD040574
Record last reviewed:  January 2005
Last Updated:  January 6, 2005
Record first received:  December 3, 2004
ClinicalTrials.gov Identifier:  NCT00098176
Health Authority: United States: Federal Government
ClinicalTrials.gov processed this record on 2005-04-08