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Home / Equine Research Bank / Wellcome Open Res / Intrathecal Immunoglobulin for treatment of adult patients w...
Wellcome open research2018; 3; 58; doi: 10.12688/wellcomeopenres.14587.2

Intrathecal Immunoglobulin for treatment of adult patients with tetanus: A randomized controlled 2×2 factorial trial.

Abstract: Despite long-standing availability of an effective vaccine, tetanus remains a significant problem in many countries. Outcome depends on access to mechanical ventilation and intensive care facilities and in settings where these are limited, mortality remains high. Administration of tetanus antitoxin by the intramuscular route is recommended treatment for tetanus, but as the tetanus toxin acts within the central nervous system, it has been suggested that intrathecal administration of antitoxin may be beneficial. Previous studies have indicated benefit, but with the exception of one small trial no blinded studies have been performed. The objective of this study is to establish whether the addition of intrathecal tetanus antitoxin reduces the need for mechanical ventilation in patients with tetanus. Secondary objectives: to determine whether the addition of intrathecal tetanus antitoxin reduces autonomic nervous system dysfunction and length of hospital/ intensive care unit stay; whether the addition of intrathecal tetanus antitoxin in the treatment of tetanus is safe and cost-effective; to provide data to inform recommendation of human rather than equine antitoxin. This study will enroll adult patients (≥16 years old) with tetanus admitted to the Hospital for Tropical Diseases, Ho Chi Minh City. The study is a 2x2 factorial blinded randomized controlled trial. Eligible patients will be randomized in a 1:1:1:1 manner to the four treatment arms (intrathecal treatment and human intramuscular treatment, intrathecal treatment and equine intramuscular treatment, sham procedure and human intramuscular treatment, sham procedure and equine intramuscular treatment). Primary outcome measure will be requirement for mechanical ventilation. Secondary outcome measures: duration of hospital/ intensive care unit stay, duration of mechanical ventilation, in-hospital and 240-day mortality and disability, new antibiotic prescription, incidence of ventilator associated pneumonia and autonomic nervous system dysfunction, total dose of benzodiazepines and pipecuronium, and incidence of adverse events. ClinicalTrials.gov NCT02999815 21 December 2016.
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Publication Date: 2018-11-05 PubMed ID: 30809591PubMed Central: PMC6372971DOI: 10.12688/wellcomeopenres.14587.2Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

This research investigates the effectiveness of introducing an antitoxin directly into the spinal fluid (intrathecal administration) for treating adult patients with tetanus. The study specifically aims to see if this method reduces the need for mechanical ventilation and improves patient outcomes.

Introduction and Background

  • Tetanus is an infectious disease, although a vaccine is available, it remains a widespread problem particularly in developing countries. The patient’s outcome typically depends on the availability and access to modern medical technologies such as mechanical ventilators and intensive care facilities. Mortality rates are high where such facilities are limited.
  • The conventional mode of treatment for tetanus involves the intramuscular administration of tetanus antitoxin. But since the tetanus toxin particularly affects the central nervous system, there has been a hypothesis stating the potential benefits of directly delivering the antitoxin into the spinal fluid through a procedure called intrathecal administration.
  • Previous studies indicated a potential benefit from this method of administration, but there has been only one small-scale blinded trial conducted so far, prompting the need for a larger, rigorous study.

Objective and Methodology

  • The primary objective of the study at hand is to verify whether intrathecal administration of the tetanus antitoxin helps in reducing the need for mechanical ventilation in tetanus patients.
  • Secondary objectives include evaluating the effect of this procedure on autonomic nervous system dysfunction and the duration of hospital or intensive care stay. The study would also assess the safety and cost-effectiveness of the procedure, and compare the effectiveness of human and equine antitoxin.
  • To conduct this study, adult patients aged 16 and above diagnosed with tetanus would be admitted to the Hospital for Tropical Diseases in Ho Chi Minh City.
  • The study’s design is a 2×2 factorial blinded randomized controlled trial. Patients will be evenly divided into four groups with varying combinations of intrathecal and intramuscular treatments. The outcomes from these different groups will be compared to test the study hypotheses.

Outcome Measures

  • The primary outcome measure will be the necessity for mechanical ventilation. This parameter will be the primary indicator of the efficacy of intrathecal administration.
  • Secondary outcome measures cover a range of factors including the duration of hospital stay, intensive care requirement, mechanical ventilation requirement, mortality, disability incidence, new antibiotic prescriptions, incidence of ventilator-associated pneumonia, autonomic nervous system dysfunction, total benzodiazepine and pipecuronium dosage, and adverse event incidence.

Cite This Article

APA
Loan HT, Yen LM, Kestelyn E, Hao NV, Thanh TT, Dung NTP, Turner HC, Geskus RB, Wolbers M, Tan LV, Van Doorn HR, Day NP, Wyncoll D, Hien TT, Thwaites GE, Vinh Chau NV, Thwaites CL. (2018). Intrathecal Immunoglobulin for treatment of adult patients with tetanus: A randomized controlled 2×2 factorial trial. Wellcome Open Res, 3, 58. https://doi.org/10.12688/wellcomeopenres.14587.2

Publication

Wellcome open research
ISSN: 2398-502X
NlmUniqueID: 101696457
Country: England
Language: English
Volume: 3
Pages: 58
PII: 58

Researcher Affiliations

Loan, Huỳnh Thị
  • Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Yen, Lam Minh
  • Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Kestelyn, Evelyne
  • Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
  • Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, OX3 7FZ, UK.
Hao, Nguyen Van
  • Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
  • Medicine and Pharmacy, Hong Bang International University, Ho Chi Minh City, Vietnam.
Thanh, Tran Tan
  • Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Dung, Nguyen Thi Phuong
  • Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Turner, Hugo C
  • Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
  • Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, OX3 7FZ, UK.
Geskus, Ronald B
  • Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
  • Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, OX3 7FZ, UK.
Wolbers, Marcel
  • Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Tan, Le Van
  • Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Van Doorn, H Rogier
  • Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
  • Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, OX3 7FZ, UK.
Day, Nicholas P
  • Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, OX3 7FZ, UK.
  • Mahidol Oxford Research Unit, Bangkok, 10400, Thailand.
Wyncoll, Duncan
  • Guys and St Thomas' Hospitals NHS Foundation Trust, London, SE1 7EH, UK.
Hien, Tran Tinh
  • Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
  • Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, OX3 7FZ, UK.
Thwaites, Guy E
  • Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
  • Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, OX3 7FZ, UK.
Vinh Chau, Nguyen Van
  • Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
Thwaites, C Louise
  • Oxford University Clinical Research Unit, Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam.
  • Centre for Tropical Medicine and Global Health, University of Oxford, Oxford, OX3 7FZ, UK.

Grant Funding

  • Wellcome Trust

Conflict of Interest Statement

No competing interests were disclosed.

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Citations

This article has been cited 5 times.
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