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| Name | Class |
|---|---|
| Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam | OTHER |
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To establish whether the addition of intrathecal tetanus antitoxin reduces the need for mechanical ventilation in patients with tetanus
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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Human tetanus immunoglobulin | Active Comparator | Human tetanus immunoglobulin (Tetagam-P): Injection (prefilled syringe) 250 IU in 1 ml - Intrathecal 500 IU |
|
| Intramuscular antitoxin | Sham Comparator | Human tetanus immunoglobulin (Tetagam-P): Injection (prefilled syringe) 250 IU in 1 ml - Intramuscular 3000 IU OR Equine antiserum - 21,000 units |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| Human tetanus immunoglobulin | Procedure | 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. |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Minh Yen Lam, MD | Oxford University Clinical Research Unit | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Hospital for Tropical Diseases | Ho Chi Minh City | 700000 | Vietnam |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23314360 | Background | Jiang D, Pu X, Wu J, Li M, Liu P. Rapid, sensitive, and specific detection of Clostridium tetani by loop-mediated isothermal amplification assay. J Microbiol Biotechnol. 2013 Jan;23(1):1-6. doi: 10.4014/jmb.1205.05063. | |
| 15363647 | Background | Thwaites CL, Yen LM, Nga NT, Parry J, Binh NT, Loan HT, Thuy TT, Bethell D, Parry CM, White NJ, Day NP, Farrar JJ. Impact of improved vaccination programme and intensive care facilities on incidence and outcome of tetanus in southern Vietnam, 1993-2002. Trans R Soc Trop Med Hyg. 2004 Nov;98(11):671-7. doi: 10.1016/j.trstmh.2004.01.008. |
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| ID | Term |
|---|---|
| D013742 | Tetanus |
| ID | Term |
|---|---|
| D003015 | Clostridium Infections |
| D016908 | Gram-Positive Bacterial Infections |
| D001424 | Bacterial Infections |
| D001423 | Bacterial Infections and Mycoses |
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|
| Intramuscular antitoxin | Procedure | 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 |
|
| 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 | New antibiotic prescription during ICU stay (excluding antibiotics for tetanus or initial entry site infection) | During ICU stay, an average of 3 weeks |
| 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:
| During hospital stay, an average of 5 weeks |
| Incidence of clinical syndrome of autonomic nervous system dysfunction | At least 3 of the following criteria:
| 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 |
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| 35561721 | Derived | Van Hao N, Loan HT, Yen LM, Kestelyn E, Hong DD, Thuy DB, Nguyen NT, Duong HTH, Thuy TTD, Nhat PTH, Khanh PNQ, Dung NTP, Phu NH, Phong NT, Lieu PT, Tuyen PT, Hanh BTB, Nghia HDT, Oanh PKN, Tho PV, Tan Thanh T, Turner HC, van Doorn HR, Van Tan L, Wyncoll D, Day NP, Geskus RB, Thwaites GE, Van Vinh Chau N, Thwaites CL. Human versus equine intramuscular antitoxin, with or without human intrathecal antitoxin, for the treatment of adults with tetanus: a 2 x 2 factorial randomised controlled trial. Lancet Glob Health. 2022 Jun;10(6):e862-e872. doi: 10.1016/S2214-109X(22)00117-6. |
| 30809591 | Derived | Loan HT, Yen LM, Kestelyn E, Hao NV, Thanh TT, Dung NTP, Turner HC, Geskus RB, Wolbers M, Tan LV, Van Doorn HR, Day NP, Wyncoll D, Hien TT, Thwaites GE, Vinh Chau NV, Thwaites CL. Intrathecal Immunoglobulin for treatment of adult patients with tetanus: A randomized controlled 2x2 factorial trial. Wellcome Open Res. 2018 Nov 5;3:58. doi: 10.12688/wellcomeopenres.14587.2. eCollection 2018. |
| D007239 | Infections |