Intrathecal Tetanus Immunoglobulin to Treat Tetanus (ITITTT)
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| ClinicalTrials.gov Identifier: NCT02999815 |
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Recruitment Status :
Completed
First Posted : December 21, 2016
Last Update Posted : May 29, 2020
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| Condition or disease | Intervention/treatment | Phase |
|---|---|---|
| Tetanus | Procedure: Human tetanus immunoglobulin Procedure: Intramuscular antitoxin | Phase 1 Phase 2 |
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 Type : | Interventional (Clinical Trial) |
| Actual Enrollment : | 272 participants |
| Allocation: | Randomized |
| Intervention Model: | Factorial Assignment |
| Masking: | Double (Care Provider, Investigator) |
| Primary Purpose: | Treatment |
| Official Title: | Intrathecal Immunoglobulin for Treatment of Adult Patients With Tetanus: a Randomized Controlled 2x2 Factorial Trial |
| Actual Study Start Date : | February 13, 2017 |
| Actual Primary Completion Date : | December 31, 2019 |
| Actual Study Completion Date : | May 1, 2020 |
| Arm | Intervention/treatment |
|---|---|
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Active Comparator: Human tetanus immunoglobulin
Human tetanus immunoglobulin (Tetagam-P): Injection (prefilled syringe) 250 IU in 1 ml - Intrathecal 500 IU
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Procedure: Human tetanus immunoglobulin
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.
Other Name: Human tetanus immunoglobulin (Tetagam-P) |
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Sham Comparator: Intramuscular antitoxin
Human tetanus immunoglobulin (Tetagam-P): Injection (prefilled syringe) 250 IU in 1 ml - Intramuscular 3000 IU OR Equine antiserum - 21,000 units
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Procedure: Human tetanus immunoglobulin
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.
Other Name: Human tetanus immunoglobulin (Tetagam-P) Procedure: Intramuscular antitoxin 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 |
- 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.
- Duration of ICU stay [ Time Frame: During ICU stay, an average of 3 weeks ]
- Duration of hospital stay [ Time Frame: During hospital stay, an average of 5 weeks ]
- Duration of mechanical ventilation [ Time Frame: During hospital stay, an average of 5 weeks ]
- In hospital and 240 day mortality [ Time Frame: 240 days ]
- In hospital and 240 day disability [ Time Frame: 240 days ]
- New antibiotic prescription during ICU stay [ Time Frame: 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 [ Time Frame: 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 [ Time Frame: 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 hypotension
- Total dose of benzodiazepines and pipecuronium during hospital stay [ Time Frame: During hospital stay, an average of 5 weeks ]
- Incidence of adverse events [ Time Frame: During hospital stay, an average of 5 weeks ]
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| Ages Eligible for Study: | 16 Years and older (Child, Adult, Older Adult) |
| Sexes Eligible for Study: | 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
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02999815
| Vietnam | |
| Hospital for Tropical Diseases | |
| Ho Chi Minh, Vietnam, 700000 | |
| Principal Investigator: | Minh Yen Lam, MD | Oxford University Clinical Research Unit |
Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
| Responsible Party: | Oxford University Clinical Research Unit, Vietnam |
| ClinicalTrials.gov Identifier: | NCT02999815 |
| Other Study ID Numbers: |
03TS |
| First Posted: | December 21, 2016 Key Record Dates |
| Last Update Posted: | May 29, 2020 |
| Last Verified: | May 2020 |
| Individual Participant Data (IPD) Sharing Statement: | |
| Plan to Share IPD: | Undecided |
| Studies a U.S. FDA-regulated Drug Product: | No |
| Studies a U.S. FDA-regulated Device Product: | No |
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Tetanus |
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Tetanus Tetany Clostridium Infections Gram-Positive Bacterial Infections Bacterial Infections Bacterial Infections and Mycoses Infections Neuromuscular Manifestations Neurologic Manifestations Nervous System Diseases |
Hypocalcemia Calcium Metabolism Disorders Metabolic Diseases Immunoglobulins Immunoglobulins, Intravenous Antibodies Antitoxins Immunologic Factors Physiological Effects of Drugs |