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ISRCTN
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ISRCTN57194591
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ClinicalTrials.gov identifier
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Public title
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A randomised, open, comparison of penicillin and metronidazole for the treatment of tetanus
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Scientific title
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Acronym
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TS Study
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Serial number at source
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077166
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Study hypothesis
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Penicillin given parenterally has been the standard antibiotic treatment for tetanus for more than 50 years. However there are several theoretical disadvantages to its use. Because many patients with tetanus cannot take medicines orally, penicillin must be administered by injection, either IntraMuscular (IM) or IntraVenous (IV). Any noxious stimulus, such as an injection, has the potential to induce potentially lethal spasms.
Penicillin is known to block post-synaptic Gamma-AminoButyric Acid (GABA) and thus is pro-convulsant. It could lower the threshold for convulsions, which may be seen in severe tetanus. Since GABA transmission occurs in skeletal muscles as well as the central nervous system, penicillin could in theory worsen spasms as well. Metronidazole may be given rectally by suppository, thus obviating the need for painful injections. Bioavailability by this route is reasonably high. Metronidazole is known to be effective against Clostridia species. In a small study from Indonesia metronidazole was at least as effective as penicillin in patients with tetanus of moderate severity, although many patient details were not given in the published report. This study aimed to compare IV penicillin and metronidazole suppositories for the treatment of tetanus.
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Lay summary
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Ethics approval
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Not provided at time of registration
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Study design
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Randomised controlled trial
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Countries of recruitment
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Bangladesh, Thailand
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Disease/condition/study domain
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Tetanus
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Participants - inclusion criteria
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1. Clinical diagnosis of tetanus
2. Aged more than one month
3. Informed consent from patient or attendant relative (if comatose or aged less than 16 years)
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Participants - exclusion criteria
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Lack of informed consent or age less than one month
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Anticipated start date
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01/04/1993
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Anticipated end date
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01/01/1997
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Status of trial
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Completed |
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Patient information material
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Target number of participants
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To be added
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Interventions
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Patients entered into the study were randomised to receive:
1. Benzylpenicillin 2 million units (child 25,000 units/kg) IV six-hourly for seven days
2. Metronidazole 1 g (child):
a. 125 mg age four weeks to less than 12 months
b. 250 mg age one to four years
c. 500 mg age five to 12 years
Rectally (PR) eight-hourly for three days then 12-hourly for four days.
Once the patient could reliably tolerate oral medicines the appropriate dose of penicillin G or metronidazole was given by mouth instead of IV or PR, respectively. Patients who were known to be allergic to penicillin received erythromycin instead.
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Primary outcome measure(s)
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The primary endpoint was mortality.
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Secondary outcome measure(s)
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The secondary endpoints were recovery times and complication rates.
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Sources of funding
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The Wellcome Trust (UK) (grant ref: 077166)
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Trial website
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Publications
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Contact name
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Dr
LM
Yen
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Address
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c/o Dr Nick Day
Wellcome Unit
Faculty of Tropical Medicine
420/6 Rajvithi Road
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City/town
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Bangkok
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Zip/Postcode
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10400
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Country
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Thailand
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Tel
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+66 (0)2 3549172
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Fax
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+66 (0)2 3549169
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Email
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nickd@tropmedres.ac
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Sponsor
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University of Oxford (UK)
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Address
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CCVTM
Churchill Hospital
Old Road
Headington
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City/town
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Oxford
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Zip/Postcode
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OX3 7LJ
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Country
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United Kingdom
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Tel
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+44 (0)1865 857433
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Fax
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+44 (0)1865 857407
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Email
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ccvtm@clinical-medicine.oxford.ac.uk
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Sponsor website:
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http://www.jr2.ox.ac.uk/ndm/Tropical_Medicine
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Date applied
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13/09/2005
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Last edited
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11/08/2008
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Date ISRCTN assigned
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14/10/2005
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