Comparison of efficacy of a 7-day versus a 14-day course of intravenous antibiotics in the treatment of uncomplicated neonatal bacterial sepsis: study protocol of a randomized controlled non-inferiority trial

Abstract Background Neonatal sepsis is a global public health problem. There is no consensus regarding the optimum duration of antibiotics for culture-proven neonatal sepsis. Published randomized controlled trials (RCTs) comparing shorter versus longer courses of antibiotics provide low-quality evid...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sourabh Dutta, Sushma Nangia, Mamta Jajoo, Geeta Gathwala, Saudamini Nesargi, Mangalabharathi Sundaram, Praveen Kumar, Arvind Saili, Dipti Kumar, Poonam Dalal, P. N. Suman Rao, Ramya Shanmugam, Pallab Ray, Valinderjeet Singh Randhawa, Karnika Saigal, Madhu Sharma, Savitha Nagaraj, Devasena Radhakrishnan
Formato:	article
Lenguaje:	EN
Publicado:	BMC 2021
Materias:	Neonate Sepsis Blood culture Antibiotics Duration Randomized controlled trial Medicine (General) R5-920
Acceso en línea:	https://doaj.org/article/e1dde0f1783c4e9fa2699a552a377d0a
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:e1dde0f1783c4e9fa2699a552a377d0a
record_format	dspace
spelling	oai:doaj.org-article:e1dde0f1783c4e9fa2699a552a377d0a2021-12-05T12:20:12ZComparison of efficacy of a 7-day versus a 14-day course of intravenous antibiotics in the treatment of uncomplicated neonatal bacterial sepsis: study protocol of a randomized controlled non-inferiority trial10.1186/s13063-021-05785-61745-6215https://doaj.org/article/e1dde0f1783c4e9fa2699a552a377d0a2021-11-01T00:00:00Zhttps://doi.org/10.1186/s13063-021-05785-6https://doaj.org/toc/1745-6215Abstract Background Neonatal sepsis is a global public health problem. There is no consensus regarding the optimum duration of antibiotics for culture-proven neonatal sepsis. Published randomized controlled trials (RCTs) comparing shorter versus longer courses of antibiotics provide low-quality evidence with serious risk of bias. We hypothesized that among neonates with uncomplicated culture-proven sepsis, antibiotic duration of 7 days is not inferior to 14 days. Methods This is a multi-centric, parallel-group, stratified, block-randomized, active-controlled, non-inferiority trial with outcome assessment blinded. Stratification is by center and birth weight. Neonates weighing ≥1000 g at birth, with blood-culture-proven sepsis (barring Staphylococcus aureus and fungi), without conditions warranting > 14 days antibiotics, and who clinically remit, are enrolled in the RCT on day 7 of administration of sensitive antibiotics. They are randomly allocated to no further antibiotics (intervention arm: total 7 days) or 7 more days of the same antibiotics (control arm: total 14 days). Allocation is concealed by opaque, sealed envelopes. The primary outcome is “definite or probable relapse” within 21 days after antibiotic completion. Secondary outcomes include definite and probable relapses at various timepoints until day 35 post-randomization, secondary infections, and adverse events. The neonatologist adjudicating probable relapses and lab personnel are blinded. Three hundred fifty subjects will be recruited in each arm, assuming a non-inferiority margin of 7%, one-sided alpha error 5%, and power of 90%. Analysis will be per protocol and by intention-to-treat. An independent Data Safety Monitoring Board monitors adverse events and will perform one interim analysis when 50% of expected primary outcomes have occurred or 50% of subjects have completed follow-up, whichever is earlier. O’Brien-Fleming criteria will be used to stop for mid-term benefit and Pocock’s to stop for mid-term harm. A priori subgroup analyses are planned by birth weight categories, gram-stain status of pathogens, and radiological pneumonia. Discussion This trial will provide evidence to guide practice regarding optimum duration of antibiotics for culture-proven neonatal bacterial sepsis. If a 7-day regime is proved to be non-inferior to a 14-day regime, it is likely to reduce hospital stay, costs, adverse effects of drugs, and nosocomial infections. Trial registration Clinical Trials Registry India CTRI/2017/09/009743 . Registered on 13 September 2017.Sourabh DuttaSushma NangiaMamta JajooGeeta GathwalaSaudamini NesargiMangalabharathi SundaramPraveen KumarArvind SailiDipti KumarPoonam DalalP. N. Suman RaoRamya ShanmugamPallab RayValinderjeet Singh RandhawaKarnika SaigalMadhu SharmaSavitha NagarajDevasena RadhakrishnanBMCarticleNeonateSepsisBlood cultureAntibioticsDurationRandomized controlled trialMedicine (General)R5-920ENTrials, Vol 22, Iss 1, Pp 1-11 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neonate Sepsis Blood culture Antibiotics Duration Randomized controlled trial Medicine (General) R5-920
spellingShingle	Neonate Sepsis Blood culture Antibiotics Duration Randomized controlled trial Medicine (General) R5-920 Sourabh Dutta Sushma Nangia Mamta Jajoo Geeta Gathwala Saudamini Nesargi Mangalabharathi Sundaram Praveen Kumar Arvind Saili Dipti Kumar Poonam Dalal P. N. Suman Rao Ramya Shanmugam Pallab Ray Valinderjeet Singh Randhawa Karnika Saigal Madhu Sharma Savitha Nagaraj Devasena Radhakrishnan Comparison of efficacy of a 7-day versus a 14-day course of intravenous antibiotics in the treatment of uncomplicated neonatal bacterial sepsis: study protocol of a randomized controlled non-inferiority trial
description	Abstract Background Neonatal sepsis is a global public health problem. There is no consensus regarding the optimum duration of antibiotics for culture-proven neonatal sepsis. Published randomized controlled trials (RCTs) comparing shorter versus longer courses of antibiotics provide low-quality evidence with serious risk of bias. We hypothesized that among neonates with uncomplicated culture-proven sepsis, antibiotic duration of 7 days is not inferior to 14 days. Methods This is a multi-centric, parallel-group, stratified, block-randomized, active-controlled, non-inferiority trial with outcome assessment blinded. Stratification is by center and birth weight. Neonates weighing ≥1000 g at birth, with blood-culture-proven sepsis (barring Staphylococcus aureus and fungi), without conditions warranting > 14 days antibiotics, and who clinically remit, are enrolled in the RCT on day 7 of administration of sensitive antibiotics. They are randomly allocated to no further antibiotics (intervention arm: total 7 days) or 7 more days of the same antibiotics (control arm: total 14 days). Allocation is concealed by opaque, sealed envelopes. The primary outcome is “definite or probable relapse” within 21 days after antibiotic completion. Secondary outcomes include definite and probable relapses at various timepoints until day 35 post-randomization, secondary infections, and adverse events. The neonatologist adjudicating probable relapses and lab personnel are blinded. Three hundred fifty subjects will be recruited in each arm, assuming a non-inferiority margin of 7%, one-sided alpha error 5%, and power of 90%. Analysis will be per protocol and by intention-to-treat. An independent Data Safety Monitoring Board monitors adverse events and will perform one interim analysis when 50% of expected primary outcomes have occurred or 50% of subjects have completed follow-up, whichever is earlier. O’Brien-Fleming criteria will be used to stop for mid-term benefit and Pocock’s to stop for mid-term harm. A priori subgroup analyses are planned by birth weight categories, gram-stain status of pathogens, and radiological pneumonia. Discussion This trial will provide evidence to guide practice regarding optimum duration of antibiotics for culture-proven neonatal bacterial sepsis. If a 7-day regime is proved to be non-inferior to a 14-day regime, it is likely to reduce hospital stay, costs, adverse effects of drugs, and nosocomial infections. Trial registration Clinical Trials Registry India CTRI/2017/09/009743 . Registered on 13 September 2017.
format	article
author	Sourabh Dutta Sushma Nangia Mamta Jajoo Geeta Gathwala Saudamini Nesargi Mangalabharathi Sundaram Praveen Kumar Arvind Saili Dipti Kumar Poonam Dalal P. N. Suman Rao Ramya Shanmugam Pallab Ray Valinderjeet Singh Randhawa Karnika Saigal Madhu Sharma Savitha Nagaraj Devasena Radhakrishnan
author_facet	Sourabh Dutta Sushma Nangia Mamta Jajoo Geeta Gathwala Saudamini Nesargi Mangalabharathi Sundaram Praveen Kumar Arvind Saili Dipti Kumar Poonam Dalal P. N. Suman Rao Ramya Shanmugam Pallab Ray Valinderjeet Singh Randhawa Karnika Saigal Madhu Sharma Savitha Nagaraj Devasena Radhakrishnan
author_sort	Sourabh Dutta
title	Comparison of efficacy of a 7-day versus a 14-day course of intravenous antibiotics in the treatment of uncomplicated neonatal bacterial sepsis: study protocol of a randomized controlled non-inferiority trial
title_short	Comparison of efficacy of a 7-day versus a 14-day course of intravenous antibiotics in the treatment of uncomplicated neonatal bacterial sepsis: study protocol of a randomized controlled non-inferiority trial
title_full	Comparison of efficacy of a 7-day versus a 14-day course of intravenous antibiotics in the treatment of uncomplicated neonatal bacterial sepsis: study protocol of a randomized controlled non-inferiority trial
title_fullStr	Comparison of efficacy of a 7-day versus a 14-day course of intravenous antibiotics in the treatment of uncomplicated neonatal bacterial sepsis: study protocol of a randomized controlled non-inferiority trial
title_full_unstemmed	Comparison of efficacy of a 7-day versus a 14-day course of intravenous antibiotics in the treatment of uncomplicated neonatal bacterial sepsis: study protocol of a randomized controlled non-inferiority trial
title_sort	comparison of efficacy of a 7-day versus a 14-day course of intravenous antibiotics in the treatment of uncomplicated neonatal bacterial sepsis: study protocol of a randomized controlled non-inferiority trial
publisher	BMC
publishDate	2021
url	https://doaj.org/article/e1dde0f1783c4e9fa2699a552a377d0a
work_keys_str_mv	AT sourabhdutta comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial AT sushmanangia comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial AT mamtajajoo comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial AT geetagathwala comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial AT saudamininesargi comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial AT mangalabharathisundaram comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial AT praveenkumar comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial AT arvindsaili comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial AT diptikumar comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial AT poonamdalal comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial AT pnsumanrao comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial AT ramyashanmugam comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial AT pallabray comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial AT valinderjeetsinghrandhawa comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial AT karnikasaigal comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial AT madhusharma comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial AT savithanagaraj comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial AT devasenaradhakrishnan comparisonofefficacyofa7dayversusa14daycourseofintravenousantibioticsinthetreatmentofuncomplicatedneonatalbacterialsepsisstudyprotocolofarandomizedcontrollednoninferioritytrial
_version_	1718372046850752512

Comparison of efficacy of a 7-day versus a 14-day course of intravenous antibiotics in the treatment of uncomplicated neonatal bacterial sepsis: study protocol of a randomized controlled non-inferiority trial

Ejemplares similares