Contact information
Type
Scientific
Contact name
Dr LM Yen
ORCID ID
Contact details
c/o Dr Nick Day
Wellcome Unit
Faculty of Tropical Medicine
420/6 Rajvithi Road
Bangkok
10400
Thailand
+66 (0)2 3549172
nickd@tropmedres.ac
Additional identifiers
EudraCT/CTIS number
Nil known
IRAS number
ClinicalTrials.gov number
Nil known
Protocol/serial number
077166
Study information
Scientific title
A randomised, open, comparison of penicillin and metronidazole for the treatment of tetanus
Acronym
TS Study
Study hypothesis
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.
Ethics approval(s)
Not provided at time of registration
Study design
Randomised controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Study setting(s)
Not specified
Study type
Treatment
Patient information sheet
Condition
Tetanus
Intervention
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.
Intervention type
Drug
Pharmaceutical study type(s)
Phase
Not Specified
Drug/device/biological/vaccine name(s)
Penicillin and metronidazole
Primary outcome measure
The primary endpoint was mortality.
Secondary outcome measures
The secondary endpoints were recovery times and complication rates.
Overall study start date
01/04/1993
Overall study end date
01/01/1997
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
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)
Participant type(s)
Patient
Age group
Not Specified
Sex
Both
Target number of participants
To be added
Participant exclusion criteria
Lack of informed consent or age less than one month
Recruitment start date
01/04/1993
Recruitment end date
01/01/1997
Locations
Countries of recruitment
Bangladesh, Thailand
Study participating centre
c/o Dr Nick Day
Bangkok
10400
Thailand
Sponsor information
Organisation
University of Oxford (UK)
Sponsor details
CCVTM
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LJ
England
United Kingdom
+44 (0)1865 857433
ccvtm@clinical-medicine.oxford.ac.uk
Sponsor type
University/education
Website
http://www.jr2.ox.ac.uk/ndm/Tropical_Medicine
ROR
Funders
Funder type
Charity
Funder name
The Wellcome Trust (UK) (grant ref: 077166)
Alternative name(s)
Funding Body Type
Funding Body Subtype
Location
Results and Publications
Publication and dissemination plan
Not provided at time of registration
Intention to publish date
Individual participant data (IPD) sharing plan
Not provided at time of registration
IPD sharing plan summary
Not provided at time of registration
Study outputs
| Output type | Details | Date created | Date added | Peer reviewed? | Patient-facing? |
|---|---|---|---|---|---|
| Abstract results | conference abstract | 01/03/2002 | 23/10/2019 | No | No |