A randomised, open, comparison of penicillin and metronidazole for the treatment of tetanus
| ISRCTN | ISRCTN57194591 |
|---|---|
| DOI | https://doi.org/10.1186/ISRCTN57194591 |
| ClinicalTrials.gov (NCT) | Nil known |
| Clinical Trials Information System (CTIS) | Nil known |
| Protocol serial number | 077166 |
| Sponsor | University of Oxford (UK) |
| Funder | The Wellcome Trust (UK) (grant ref: 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 of protocol
Not provided at time of registration
Contact information
Dr LM Yen
Scientific
Scientific
c/o Dr Nick Day
Wellcome Unit
Faculty of Tropical Medicine
420/6 Rajvithi Road
Bangkok
10400
Thailand
| Phone | +66 (0)2 3549172 |
|---|---|
| nickd@tropmedres.ac |
Study information
| Primary study design | Interventional |
|---|---|
| Study design | Randomised controlled trial |
| Secondary study design | Randomised controlled trial |
| Scientific title | A randomised, open, comparison of penicillin and metronidazole for the treatment of tetanus |
| Study acronym | TS Study |
| Study objectives | 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 |
| Health condition(s) or problem(s) studied | 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 / device / biological / vaccine name(s) | Penicillin and metronidazole |
| Primary outcome measure(s) |
The primary endpoint was mortality. |
| Key secondary outcome measure(s) |
The secondary endpoints were recovery times and complication rates. |
| Completion date | 01/01/1997 |
Eligibility
| Participant type(s) | Patient |
|---|---|
| Age group | Not Specified |
| Sex | All |
| Key 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) |
| Key exclusion criteria | Lack of informed consent or age less than one month |
| Date of first enrolment | 01/04/1993 |
| Date of final enrolment | 01/01/1997 |
Locations
Countries of recruitment
- Bangladesh
- Thailand
Study participating centre
c/o Dr Nick Day
Bangkok
10400
Thailand
10400
Thailand
Results and Publications
| Individual participant data (IPD) Intention to share | No |
|---|---|
| IPD sharing plan summary | 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.
