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ITITTT: Intrathecal Tetanus Immunoglobulin to Treat Tetanus

Sponsor
Oxford University Clinical Research Unit, Vietnam (Other)
Overall Status
Completed
CT.gov ID
NCT02999815
Collaborator
Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam (Other)
272
Enrollment
1
Location
2
Arms
38.5
Actual Duration (Months)
7.1
Patients Per Site Per Month

Study Details

Study Description

Brief Summary

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

Condition or Disease Intervention/Treatment Phase
  • Procedure: Human tetanus immunoglobulin
  • Procedure: Intramuscular antitoxin
 Phase 1/Phase 2

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 Design

Study Type:
Interventional
Actual Enrollment :
272 participants
Allocation:
Randomized
Intervention Model:
Factorial Assignment
Masking:
Double (Care Provider, Investigator)
Primary Purpose:
Treatment
Official Title:
Intrathecal Immunoglobulin for Treatment of Adult Patients With Tetanus: a Randomized Controlled 2x2 Factorial Trial
Actual Study Start Date :
Feb 13, 2017
Actual Primary Completion Date :
Dec 31, 2019
Actual Study Completion Date :
May 1, 2020

Arms and Interventions

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

    Outcome Measures

    Primary Outcome Measures

    1. Requirement for mechanical ventilation during ICU stay [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 Outcome Measures

    1. Duration of ICU stay [During ICU stay, an average of 3 weeks]

    2. Duration of hospital stay [During hospital stay, an average of 5 weeks]

    3. Duration of mechanical ventilation [During hospital stay, an average of 5 weeks]

    4. In hospital and 240 day mortality [240 days]

    5. In hospital and 240 day disability [240 days]

    6. New antibiotic prescription during ICU stay [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 [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 [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 [During hospital stay, an average of 5 weeks]

    10. Incidence of adverse events [During hospital stay, an average of 5 weeks]

    Eligibility Criteria

    Criteria

    Ages Eligible for Study:
    16 Years and Older
    Sexes Eligible for Study:
    All
    Accepts Healthy Volunteers:
    No
    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

    Contacts and Locations

    Locations

    Site City State Country Postal Code
    1 Hospital for Tropical Diseases Ho Chi Minh Vietnam 700000

    Sponsors and Collaborators

    • Oxford University Clinical Research Unit, Vietnam
    • Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

    Investigators

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

    Study Documents (Full-Text)

    None provided.

    More Information

    Publications

    Responsible Party:
    Oxford University Clinical Research Unit, Vietnam
    ClinicalTrials.gov Identifier:
    NCT02999815
    Other Study ID Numbers:
    • 03TS
    First Posted:
    Dec 21, 2016
    Last Update Posted:
    May 29, 2020
    Last Verified:
    May 1, 2020
    Individual Participant Data (IPD) Sharing Statement:
    Undecided
    Plan to Share IPD:
    Undecided
    Studies a U.S. FDA-regulated Drug Product:
    No
    Studies a U.S. FDA-regulated Device Product:
    No
    Keywords provided by Oxford University Clinical Research Unit, Vietnam
    Tetanus
    Additional relevant MeSH terms:
    Tetanus
    Tetany
    Immunoglobulins
    Immunoglobulins, Intravenous
    Antibodies
    Antitoxins

    Study Results

    No Results Posted as of May 29, 2020