Intrathecal Tetanus Immunoglobulin to Treat Tetanus

Tetanus Clinical Trial

— ITITTT  

Official title:

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

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT02999815
• Other study ID #: 03TS
• Status: Completed
• Phase: Phase 1/Phase 2
• Start date: February 13, 2017
• Est. completion date: May 1, 2020

Study information

• Verified date: May 2020
• Source: Oxford University Clinical Research Unit, Vietnam
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

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

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.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 272
• Est. completion date: May 1, 2020
• Est. primary completion date: December 31, 2019
• Accepts healthy volunteers: No
• Gender: All
• Age group: 16 Years and older

Eligibility

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

Related Conditions & MeSH terms

• Tetanus

Intervention

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.
• 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

Locations

Country	Name	City	State
Vietnam	Hospital for Tropical Diseases	Ho Chi Minh

Sponsors (2)

Lead Sponsor	Collaborator
Oxford University Clinical Research Unit, Vietnam	Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

Country where clinical trial is conducted

Vietnam, 

References & Publications (55)

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* Note: There are 55 references in all — Click here to view all references

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Requirement for mechanical ventilation during ICU stay	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	Duration of ICU stay		During ICU stay, an average of 3 weeks
Secondary	Duration of hospital stay		During hospital stay, an average of 5 weeks
Secondary	Duration of mechanical ventilation		During hospital stay, an average of 5 weeks
Secondary	In hospital and 240 day mortality		240 days
Secondary	In hospital and 240 day disability		240 days
Secondary	New antibiotic prescription during ICU stay	New antibiotic prescription during ICU stay (excluding antibiotics for tetanus or initial entry site infection)	During ICU stay, an average of 3 weeks
Secondary	Incidence of Ventilator Associated Pneumonia	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
Secondary	Incidence of clinical syndrome of autonomic nervous system dysfunction	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
Secondary	Total dose of benzodiazepines and pipecuronium during hospital stay		During hospital stay, an average of 5 weeks
Secondary	Incidence of adverse events		During hospital stay, an average of 5 weeks