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Completed

NCT Number: NCT02999815

Intrathecal Tetanus Immunoglobulin to Treat Tetanus

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

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Key information

Conditions

Tetanus Bacterial Infections Bacterial Infections and Mycoses Clostridium Infections Gram-Positive Bacterial Infections Infections

Age range

16 year and older

Sex eligibility

All sexes

Study type

Interventional

Phase

Phase 1 / Phase 2

Primary location

Hospital for Tropical Diseases

Ho Chi Minh City, 700000, Vietnam

About this study

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.

Who can participate

Healthy volunteers accepted: No

Only the study team can determine whether someone qualifies for participation.

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

Treatment and study plan

Human tetanus immunoglobulin

Procedure

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)

Intramuscular antitoxin

Procedure

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

Primary outcomes

  1. 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.

Secondary outcomes

  1. Duration of ICU stay

    Time frame: During ICU stay, an average of 3 weeks

  2. Duration of hospital stay

    Time frame: During hospital stay, an average of 5 weeks

  3. Duration of mechanical ventilation

    Time frame: During hospital stay, an average of 5 weeks

  4. In hospital and 240 day mortality

    Time frame: 240 days

  5. In hospital and 240 day disability

    Time frame: 240 days

  6. 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)

  7. 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))

  8. 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

  9. Total dose of benzodiazepines and pipecuronium during hospital stay

    Time frame: During hospital stay, an average of 5 weeks

  10. Incidence of adverse events

    Time frame: During hospital stay, an average of 5 weeks

Sponsors and collaborators

Lead sponsor

Oxford University Clinical Research Unit, Vietnam

Other

Collaborators

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

Registry information

Official study title

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

Acronym: ITITTT

Important dates

Study start
2017
Primary completion
2019
Study completion
2020
First posted
Dec 21, 2016
Registry last updated
May 29, 2020

OpenTrials presents study information sourced from ClinicalTrials.gov. The official registry record should be consulted for the latest information.

View the official ClinicalTrials.gov record (opens in a new tab)

This listing is for discovery and informational purposes only. It is not medical advice, does not guarantee that a study is recruiting, and does not determine eligibility. Contact the study team and a qualified healthcare professional when considering participation.

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