Condition category
Infections and Infestations
Date applied
13/09/2005
Date assigned
14/10/2005
Last edited
11/08/2008
Prospective/Retrospective
Retrospectively registered
Overall trial status
Completed
Recruitment status
No longer recruiting

Plain English Summary

Not provided at time of registration

Trial website

Contact information

Type

Scientific

Primary contact

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 number

ClinicalTrials.gov number

Protocol/serial number

077166

Study information

Scientific title

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

Not provided at time of registration

Study design

Randomised controlled trial

Primary study design

Interventional

Secondary study design

Randomised controlled trial

Trial setting

Not specified

Trial 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

Phase

Not Specified

Drug names

Penicillin and metronidazole

Primary outcome measures

The primary endpoint was mortality.

Secondary outcome measures

The secondary endpoints were recovery times and complication rates.

Overall trial start date

01/04/1993

Overall trial end date

01/01/1997

Reason abandoned

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

Patient

Age group

Not Specified

Gender

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

Trial 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
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

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

Participant level data

Not provided at time of registration

Results - basic reporting

Publication summary

Publication citations

Additional files

Editorial Notes