A Phase 3 interventional study of 7-day course of antibiotics and 14-day course of antibiotics in Infant, Newborn, Neonatal SEPSIS and Anti-bacterial Agents, sponsored by Indian Council of Medical Research. Completed at 7 sites in India. Open to participants aged 1 Hour to 28 Days. Per ClinicalTrials.gov, last updated 2023-11-02.
Sponsored by Indian Council of Medical Research · Phase 3, Interventional, and Treatment
The optimum duration of intravenous antibiotic therapy for culture-proven neonatal bacterial sepsis is not known. Current practices, ranging from 7 days to 14 days of antibiotics, are not evidence-based. This is a randomized, active -controlled, multi-centric, non-inferiority trial to compare the efficacy of a 7-day course of intravenous antibiotics versus a 14-day course among neonates weighing > 1000 g at birth with culture-proven bacterial sepsis that is uncomplicated by meningitis, bone or joint infections deep-seated abscesses. The primary outcome measure is a definite or probable relapse within 21 days after stoppage of antibiotics.
The optimum duration of intravenous antibiotic therapy for uncomplicated neonatal bacterial septicemia is not known. Pediatricians administer anywhere between 7 to 14 days of antibiotics, but these practices are not evidence based. C reactive protein (CRP) guided antibiotic duration is based on limited data and serial quantitative CRP is both cumbersome and not universally available. If it could be demonstrated that a 7-day course of antibiotics is not inferior to a 14-day course of antibiotics in terms of relapse rates of infection, then a 7 day course of antibiotics could be uniformly adopted, resulting in economic savings, shorter duration of hospitalization, less chances of hospital acquired infections, less chances of antibiotic induced adverse events and less antibiotic resistance. To test this hypothesis, a randomized, active-controlled, multi-centric, non-inferiority trial to compare the efficacy of a 7-day course of intravenous antibiotics with a 14-day course has been planned. Subjects weighing more than 1000 g at birth with suspected sepsis will be enrolled and observed for a 7-day period to see if they meet eligibility criteria for randomization. Subjects will be randomized on the 7th day of antibiotics, if the initial blood culture grows a non-Staphylococcus aureus bacterial organism, if they have no meningitis, osteomyelitis, septic arthritis or deep seated abscess and if the sepsis goes into clinical remission by the 5th day and remains in remission up to the 7th day of sensitive antibiotics. Subjects in the 14-day group will receive 7 more days of antibiotics after randomization, whereas those in the 7-day group will receive no further antibiotics after randomization. Subjects will be followed up for a 35-day period after randomization. The key outcome will be treatment failure as measured by "definite or probable relapse" within a 21-day period after completion of antibiotic therapy. Secondary outcomes will include definite relapse within 21 and 28 days after antibiotic completion and within 28 and 35 days after randomization; and probable relapse at similar time points. Other secondary outcomes will include secondary infections and adverse events. A total sample size of 700 (350 in each arm) will be required to detect a non-inferiority margin of 7%, assumed event rate of 10%, with 90% power, one-sided alpha error of 5% and loss to follow-up of approximately 10%. Data safety monitoring board will monitor serious adverse events in the trial and will perform at 1/3rd and 2/3rd of expected recruitment. At the time of interim analysis, the DSMB will revisit the sample size of the study. O'Brien Fleming's stopping criteria will be used for the primary outcome while Pocock's stopping rule will be used for the serious adverse events.
Inclusion criteria for the initial observation part of study preceding randomization
Inclusion criteria for Randomization applicable after 7 days of therapy of above patients with sensitive antibiotics:
Exclusion Criteria:
Exclusion criteria for the initial observation part of study preceding randomization:
Exclusion criteria for randomization applicable after 7 days of therapy of above patients with sensitive antibiotics:
Randomization of subjects will be performed at the end of 7 days of sensitive intravenous antibiotic administration, provided the subjects meet randomization criteria. Those who are randomized to the 7-day group will not receive any further antibiotics.
Drug: 7-day course of antibiotics
Randomization of subjects will be performed at the end of 7 days of sensitive intravenous antibiotic administration, provided the subjects meet randomization criteria. Those who are randomized to the 14-day group will receive 7 more days of the same antibiotics, to make it a total of 14 days.
Drug: 14-day course of antibiotics
Subjects in the "7-day course of antibiotics" arm of the study will receive no further antibiotics after randomization as they would have already received 7 days of sensitive antibiotics before randomization. The choice of antibiotics would be guided by the blood culture and sensitivity report. Thus, subjects in this arm of the study could get a variety of antibiotics, depending on the sensitivity reports. Hence, names of specific antibiotics and/or their brand names have not been mentioned.
Subjects in the "14-day course of antibiotics" arm of the study will receive 7 more days of antibiotics after randomization as they would have already received 7 days of sensitive antibiotics before randomization. The choice of antibiotics would be guided by the blood culture and sensitivity report. Thus, subjects in this arm of the study could get a variety of antibiotics, depending on the sensitivity reports. Hence, names of specific antibiotics and/or their brand names have not been mentioned.
Definite or probable relapse within 21 days post-antibiotic completion as per protocol
Among participants who adhered to study protocol- Definite relapse: Episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode, Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
Time frame: From 0-21 days after the end of the planned antibiotic therapy
Definite or probable relapse within 21 days post-antibiotic completion as per intention to treat
Among all randomized patients- Definite relapse: Episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode, Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
Time frame: From 0-21 days after the end of the planned antibiotic therapy
Definite relapse within 21 days post-antibiotic completion, as per protocol
Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
Time frame: From 0-21 days after the end of the planned antibiotic therapy
Definite relapse within 21 days post-antibiotic completion, as per intention-to-treat
Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
Time frame: From 0-21 days after the end of the planned antibiotic therapy
Definite relapse within 28 days post-antibiotic completion, as per protocol
Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
Time frame: From 0-28 days after the end of the planned antibiotic therapy
Definite relapse within 28 days post-antibiotic completion, as per intention-to-treat
Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
Time frame: From 0-28 days after the end of the planned antibiotic therapy
Definite relapse within 28 days post-randomization, as per protocol
Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
Time frame: From 0-28 days after randomization
Definite relapse within 28 days post-randomization, as per Intention-to-treat
Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
Time frame: From 0-28 days after randomization
Definite relapse within 35 days post-randomization, as per protocol
Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
Time frame: From 0-35 days after randomization
Definite relapse within 35 days post-randomization, as per intention to treat
Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode
Time frame: From 0-35 days after randomization
Probable relapse within 21 days post-antibiotic completion, as per protocol
Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
Time frame: From 0-21 days after the end of the planned antibiotic therapy
Probable relapse within 21 days post-antibiotic completion, as per intention-to-treat
Among all randomized patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
Time frame: From 0-21 days after the end of the planned antibiotic therapy
Probable relapse within 28 days post-antibiotic completion, as per protocol
Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
Time frame: From 0-28 days after the end of the planned antibiotic therapy
Probable relapse within 28 days post-antibiotic completion, as per intention-to-treat
Among all randomized patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
Time frame: From 0-28 days after the end of the planned antibiotic therapy
Probable relapse within 28 days post-randomization, as per protocol
Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
Time frame: From 0-28 days after randomization
Probable relapse within 28 days post-randomization, as per intention-to-treat
Among all randomized patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
Time frame: From 0-28 days after randomization
Probable relapse within 35 days post-randomization, as per protocol
Among participants who adhered to study protocol Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
Time frame: From 0-35 days after randomization
Probable relapse within 35 days post-randomization, as per intention-to-treat
Among all randomised patients Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
Time frame: From 0-35 days after randomization
Definite relapse or probable relapse within 28 days post-randomization, as per protocol
Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
Time frame: From 0-28 days after randomization
Definite relapse or probable relapse within 28 days post-randomization, as per Intention-to-treat
Among all randomized patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
Time frame: From 0-28 days after randomization
Definite relapse or probable relapse within 35 days post-randomization, as per protocol
Among participants who adhered to study protocol Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
Time frame: From 0-35 days after randomization
Definite relapse or probable relapse within 35 days post-randomization, as per intention-to-treat
Among all randomised patients Definite relapse defined as: episode of blood-culture-positive relapse of neonatal sepsis caused by the same organism having the same antibiogram as the original episode Probable relapse: episode of illness without positive cultures adjudicated by a blinded adjudicator to be a relapse of the original episode of sepsis.
Time frame: From 0-35 days after randomization
Secondary sepsis
Sepsis due to bacterial organisms other than the original etiologic bacteria or with a different antibiogram or with a fungal organism
Time frame: From 0-35 days after randomization
Adverse events
Adverse events as per a list of adverse events, graded as per severity, and defined a priori
Time frame: From 0-35 days after randomization
Documents are hosted by the registry — open the source record to download them.
Plan to share: No
This study is completed, as verified in Oct 2023. You cannot join it, but the record below documents what was studied.
Get an email when the registry record changes — status, dates, results — or when someone posts here.
Sign in to followQuestions and observations about this study, from anyone following it. Not medical advice, and not a channel to the study team — their contact details are on the registry record.
Sign in to join the discussion. Reading takes no account; posting does. You choose a display name, and a pseudonym is the default.
Nothing here yet. If you are running this trial, taking part in it, or weighing whether to, this is the place to say so.
Indian Council of Medical Research