Intrathecal Immunoglobulin for Treatment of Adult Patients With Tetanus: a Randomized Controlled 2x2 Factorial Trial
Trial Snapshot
- Phase
- Phase 1
- Status
- Completed
- Enrollment
- 272
- Locations
- 2
- Primary Endpoint
- Requirement for mechanical ventilation during ICU stay
Study Overview
Brief Summary
To establish whether the addition of intrathecal tetanus antitoxin reduces the need for mechanical ventilation in patients with tetanus
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
- Allocation
- Randomized
- Intervention Model
- Factorial
- Primary Purpose
- Treatment
- Masking
- Double (Care Provider, Investigator)
Eligibility Criteria
- Ages
- 16 Years to — (Child, Adult, Older Adult)
- Sex
- 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
Outcomes
Primary Outcomes
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
- Duration of ICU stay(During ICU stay, an average of 3 weeks)
- Duration of hospital stay(During hospital stay, an average of 5 weeks)
- Duration of mechanical ventilation(During hospital stay, an average of 5 weeks)
- In hospital and 240 day mortality(240 days)
- In hospital and 240 day disability(240 days)
- New antibiotic prescription during ICU stay(During ICU stay, an average of 3 weeks)
- Incidence of Ventilator Associated Pneumonia(During hospital stay, an average of 5 weeks)
- Incidence of clinical syndrome of autonomic nervous system dysfunction(240 days)
- Total dose of benzodiazepines and pipecuronium during hospital stay(During hospital stay, an average of 5 weeks)
- Incidence of adverse events(During hospital stay, an average of 5 weeks)