Clinical trial NCT02999815: Intrathecal Tetanus Immunoglobulin to Treat Tetanus
Official title: Intrathecal Immunoglobulin for Treatment of Adult Patients With Tetanus: a Randomized Controlled 2x2 Factorial Trial
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Tetanus
Keywords: Tetanus
Lead sponsor: Oxford University Clinical Research Unit, Vietnam
Sponsor class: OTHER
Collaborators: name: Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
First posted: 2016-12-21
Enrollment: 272
Sex: ALL
Minimum age (years): 16
Standard ages: CHILD
ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: FACTORIAL
Primary purpose: TREATMENT

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.

Eligibility criteria: 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

Primary outcomes:
measure: Requirement for mechanical ventilation during ICU stay
timeFrame: During ICU stay, an average of 3 weeks
Secondary outcomes:
measure: Duration of ICU stay
timeFrame: During ICU stay, an average of 3 weeks
measure: Duration of hospital stay
timeFrame: During hospital stay, an average of 5 weeks
measure: Duration of mechanical ventilation
timeFrame: During hospital stay, an average of 5 weeks
measure: In hospital and 240 day mortality
timeFrame: 240 days
measure: In hospital and 240 day disability
timeFrame: 240 days
measure: New antibiotic prescription during ICU stay
timeFrame: During ICU stay, an average of 3 weeks
measure: Incidence of Ventilator Associated Pneumonia
timeFrame: During hospital stay, an average of 5 weeks
measure: Incidence of clinical syndrome of autonomic nervous system dysfunction
timeFrame: 240 days
measure: Total dose of benzodiazepines and pipecuronium during hospital stay
timeFrame: During hospital stay, an average of 5 weeks
measure: Incidence of adverse events
timeFrame: During hospital stay, an average of 5 weeks
Other outcomes:
Locations:
city: Ho Chi Minh
country: Vietnam
facility: Hospital for Tropical Diseases
Study officials:
affiliation: Oxford University Clinical Research Unit
name: Minh Yen Lam, MD
role: PRINCIPAL_INVESTIGATOR
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