Intrathecal Tetanus Immunoglobulin to Treat Tetanus (ITITTT)

May 28, 2020 updated by: Oxford University Clinical Research Unit, Vietnam

Intrathecal Immunoglobulin for Treatment of Adult Patients With Tetanus: a Randomized Controlled 2x2 Factorial Trial

To establish whether the addition of intrathecal tetanus antitoxin reduces the need for mechanical ventilation in patients with tetanus

Study Overview

Status

Completed

Conditions

Intervention / Treatment

Detailed Description

The investigators will conduct a randomised partially-blinded controlled 2x2 factorial trial. First, adults admitted to the Intensive Care Unit at the Hospital for Tropical Diseases Ho Chi Minh City will be randomized to receive either human (3000 IU) or equine (21,000 units) intramuscular antitoxin. Second, participants will be randomized to receive either standard treatment with intramuscular antitoxin alone or with the addition of 500 IU intrathecal human antitoxin. Patients with prior antitoxin treatment and those with contra-indications to lumbar puncture or antitoxin treatment will be excluded.

All patients will receive other standard tetanus treatment as deemed necessary by the attending physicians. Spasms will be treated with benzodiazepines as first-line therapy. Patients with spasms not controlled with benzodiazepines will receive tracheostomy, paralysis, magnesium sulphate and mechanical ventilation. Heart rate, BP, temperature and daily drug use will be recorded throughout the ICU stay. Patients will be followed following discharge from hospital until 240 days for disability/ death.

Study Type

Interventional

Enrollment (Actual)

272

Phase

  • Phase 2
  • Phase 1

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Vietnam
      • Ho Chi Minh, Vietnam, 700000
        • Hospital for Tropical Diseases

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Ages Eligible for Study

14 years and older (Child, Adult, Older Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • All adult patients (≥16 years old) with a clinical diagnosis of generalized tetanus admitted to the intensive care unit (ICU) at the Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

Exclusion Criteria:

  • Prior administration of antitoxin during this episode
  • Contra-indication to use of human or equine antitoxin
  • Contra-indication to lumbar puncture
  • Already receiving mechanical ventilation or expected to require this before intrathecal injection can be given
  • Pregnancy
  • Informed consent not obtained

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Treatment
  • Allocation: Randomized
  • Interventional Model: Factorial Assignment
  • Masking: Double

Arms and Interventions

Participant Group / Arm
Intervention / Treatment
Active Comparator: Human tetanus immunoglobulin
Human tetanus immunoglobulin (Tetagam-P): Injection (prefilled syringe) 250 IU in 1 ml - Intrathecal 500 IU
Procedure: Human tetanus immunoglobulin
Adults admitted to ICU at Hospital for Tropical Diseases will be randomized to receive either human (3000 IU) or equine (21,000 units) intramuscular antitoxin. Second, participants will be randomized to receive the addition of 500 IU intrathecal human antitoxin.
Other Names:
  • Human tetanus immunoglobulin (Tetagam-P)
Sham Comparator: Intramuscular antitoxin
Human tetanus immunoglobulin (Tetagam-P): Injection (prefilled syringe) 250 IU in 1 ml - Intramuscular 3000 IU OR Equine antiserum - 21,000 units
Procedure: Human tetanus immunoglobulin
Adults admitted to ICU at Hospital for Tropical Diseases will be randomized to receive either human (3000 IU) or equine (21,000 units) intramuscular antitoxin. Second, participants will be randomized to receive the addition of 500 IU intrathecal human antitoxin.
Other Names:
  • Human tetanus immunoglobulin (Tetagam-P)
Procedure: Intramuscular antitoxin
First, adults admitted to ICU at Hospital for Tropical Diseases will be randomized to receive either human (3000 IU) or equine (21,000 units) intramuscular antitoxin including a 0.05ml test dose (ie 75 units equine antitoxin or 12.5 IU human antitoxin). Second, participants will be randomized with sham procedure

What is the study measuring?

Primary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Requirement for mechanical ventilation during ICU stay
Time Frame: During ICU stay, an average of 3 weeks

Criteria for mechanical ventilation are oxygen saturation (SpO2) <90%; or partial pressure of oxygen/fraction of inspired oxygen (PaO2/FiO2) <250; or excessive spasms necessitating muscle paralysis.

These criteria are intended as a guide and the final decision to ventilate a patient rests with the individual doctor responsible for the patient.
During ICU stay, an average of 3 weeks

Secondary Outcome Measures

Outcome Measure
Measure Description
Time Frame
Duration of ICU stay
Time Frame: During ICU stay, an average of 3 weeks
During ICU stay, an average of 3 weeks
Duration of hospital stay
Time Frame: During hospital stay, an average of 5 weeks
During hospital stay, an average of 5 weeks
Duration of mechanical ventilation
Time Frame: During hospital stay, an average of 5 weeks
During hospital stay, an average of 5 weeks
In hospital and 240 day mortality
Time Frame: 240 days
240 days
In hospital and 240 day disability
Time Frame: 240 days
240 days
New antibiotic prescription during ICU stay
Time Frame: During ICU stay, an average of 3 weeks
New antibiotic prescription during ICU stay (excluding antibiotics for tetanus or initial entry site infection)
During ICU stay, an average of 3 weeks
Incidence of Ventilator Associated Pneumonia
Time Frame: During hospital stay, an average of 5 weeks

Definition of Ventilator associated pneumonia (VAP):

Mechanical ventilation for at least 48 hours and with the tube in place within the last 48 hours and 2 of:

  • Temperature > 38°C or < 36°C
  • White blood cell count <4.0 x 109/L or ≥12 x 109/L
  • Purulent respiratory secretions
  • New or progressive changes on chest radiography (for VAP) Plus for microbiologically confirmed VAP
  • Bacterial growth of ≥105 cfu/ml from endotracheal aspirate (ETA) (or ≥104 cfu/ml from Broncho Alveolar Lavage (BAL))
During hospital stay, an average of 5 weeks
Incidence of clinical syndrome of autonomic nervous system dysfunction
Time Frame: 240 days

At least 3 of the following criteria:

  • Tachycardia Heart Rate (HR)> 100 bpm
  • Hypertension Systolic Blood Pressure (SBP) > 140 mmHg
  • Hypotension Mean Arterial Pressure (MAP) < 60 mmHg
  • Pyrexia > 38°C
  • Alteration between hypertension and hypotension
240 days
Total dose of benzodiazepines and pipecuronium during hospital stay
Time Frame: During hospital stay, an average of 5 weeks
During hospital stay, an average of 5 weeks
Incidence of adverse events
Time Frame: During hospital stay, an average of 5 weeks
During hospital stay, an average of 5 weeks

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Oxford University Clinical Research Unit, Vietnam

Collaborators

Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

Investigators

  • Principal Investigator: Minh Yen Lam, MD, Oxford University Clinical Research Unit

Publications and helpful links

The person responsible for entering information about the study voluntarily provides these publications. These may be about anything related to the study.

General Publications

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start (Actual)

February 13, 2017

Primary Completion (Actual)

December 31, 2019

Study Completion (Actual)

May 1, 2020

Study Registration Dates

First Submitted

December 14, 2016

First Submitted That Met QC Criteria

December 18, 2016

First Posted (Estimate)

December 21, 2016

Study Record Updates

Last Update Posted (Actual)

May 29, 2020

Last Update Submitted That Met QC Criteria

May 28, 2020

Last Verified

May 1, 2020

More Information

Terms related to this study

Keywords

Additional Relevant MeSH Terms

Other Study ID Numbers

  • 03TS

Plan for Individual participant data (IPD)

Plan to Share Individual Participant Data (IPD)?

Undecided

Drug and device information, study documents

Studies a U.S. FDA-regulated drug product

No

Studies a U.S. FDA-regulated device product

No

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

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