A randomised, open, comparison of penicillin and metronidazole for the treatment of tetanus

ISRCTN	ISRCTN57194591
DOI	https://doi.org/10.1186/ISRCTN57194591
Secondary identifying numbers	077166

Submission date: 13/09/2005
Registration date: 14/10/2005
Last edited: 25/10/2022

Recruitment status: No longer recruiting
Overall study status: Completed
Condition category: Infections and Infestations

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Plain English Summary

Not provided at time of registration

Contact information

Dr LM Yen
Scientific

c/o Dr Nick Day
Wellcome Unit
Faculty of Tropical Medicine
420/6 Rajvithi Road
Bangkok
10400
Thailand

Phone	+66 (0)2 3549172
Email	nickd@tropmedres.ac

Study information

Study design	Randomised controlled trial
Primary study design	Interventional
Secondary study design	Randomised controlled trial
Study setting(s)	Not specified
Study type	Treatment
Scientific title	A randomised, open, comparison of penicillin and metronidazole for the treatment of tetanus
Study 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
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

Eligibility

Participant type(s)	Patient
Age group	Not Specified
Sex	Both
Target number of participants	To be added
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 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

University of Oxford (UK)
University/education

CCVTM
Churchill Hospital
Old Road
Headington
Oxford
OX3 7LJ
England
United Kingdom

Phone	+44 (0)1865 857433
Email	ccvtm@clinical-medicine.oxford.ac.uk
Website	http://www.jr2.ox.ac.uk/ndm/Tropical_Medicine
"ROR"	https://ror.org/052gg0110

Funders

Funder type

Charity

The Wellcome Trust (UK) (grant ref: 077166)

No information available

Results and Publications

Intention to publish date
Individual participant data (IPD) Intention to share	No
IPD sharing plan summary	Not provided at time of registration
Publication and dissemination plan	Not provided at time of registration
IPD sharing plan	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

Editorial Notes

25/10/2022: Internal review.
NHW 23/10/2019: Publication reference added.