Intrathecal Tetanus Immunoglobulin to Treat Tetanus (ITITTT)

Oxford University Clinical Research Unit, Vietnam

Status and phase: Completed; Phase 2; Phase 1

Conditions: Tetanus

Treatments: Procedure: Intramuscular antitoxin; Procedure: Human tetanus immunoglobulin

Study type: Interventional

Funder types: Other

Identifiers

NCT02999815

03TS

Details and patient eligibility

About

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

Full 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.

Enrollment: 272 patients

Sex: All

Ages: 16+ years old

Volunteers: No Healthy Volunteers

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

Trial design

Primary purpose: Treatment

Allocation: Randomized

Interventional model: Factorial Assignment

Masking: Double Blind

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272 participants in 2 patient groups

Human tetanus immunoglobulin

Active Comparator group

Description:

Human tetanus immunoglobulin (Tetagam-P): Injection (prefilled syringe) 250 IU in 1 ml - Intrathecal 500 IU

Treatment:

Procedure: Human tetanus immunoglobulin

Intramuscular antitoxin

Sham Comparator group

Description:

Human tetanus immunoglobulin (Tetagam-P): Injection (prefilled syringe) 250 IU in 1 ml - Intramuscular 3000 IU OR Equine antiserum - 21,000 units

Treatment:

Procedure: Human tetanus immunoglobulin

Procedure: Intramuscular antitoxin