Intrathecal Tetanus Immunoglobulin to Treat Tetanus
- Conditions
- Tetanus
- Interventions
- Procedure: Human tetanus immunoglobulinProcedure: Intramuscular antitoxin
- Registration Number
- NCT02999815
- 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.
Recruitment & Eligibility
- Status
- COMPLETED
- Sex
- All
- Target Recruitment
- 272
- 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
- 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 & Design
- Study Type
- INTERVENTIONAL
- Study Design
- FACTORIAL
- Arm && Interventions
Group Intervention Description Human tetanus immunoglobulin Human tetanus immunoglobulin Human tetanus immunoglobulin (Tetagam-P): Injection (prefilled syringe) 250 IU in 1 ml - Intrathecal 500 IU Intramuscular antitoxin Human tetanus immunoglobulin Human tetanus immunoglobulin (Tetagam-P): Injection (prefilled syringe) 250 IU in 1 ml - Intramuscular 3000 IU OR Equine antiserum - 21,000 units Intramuscular antitoxin Intramuscular antitoxin Human tetanus immunoglobulin (Tetagam-P): Injection (prefilled syringe) 250 IU in 1 ml - Intramuscular 3000 IU OR Equine antiserum - 21,000 units
- Primary Outcome Measures
Name Time Method 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
Name Time Method 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 New antibiotic prescription during ICU stay (excluding antibiotics for tetanus or initial entry site infection)
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))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 hypotensionTotal 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
Trial Locations
- Locations (1)
Hospital for Tropical Diseases
🇻🇳Ho Chi Minh, Vietnam