PlaguePhase 2/3NCT00128466
Treatment and Diagnosis of Plague
A Phase 2/3 study testing gentamicin and streptomycin in people with Plague, run by Centers for Disease Control and Prevention at 1 site in Madagascar.
Trial summary
This clinical trial will compare the effectiveness of streptomycin, which historically is the standard drug for treatment of plague, with gentamicin. The hypothesis is that gentamicin is not inferior to streptomycin but that it will have less severe side effects. Read more about this study
- Who is it for?
- Ages 2 years and older
- Conditions the study is for
- Plague
- What is being tested?
- gentamicin and streptomycin
- How many people
- 114 participants
- Where
- 1 siteMadagascar
- Study dates
- Aug 2004to Feb 2007
- Phase
- Phase 2/3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 2 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- 2 years of age or older.
- Patients must have had potential exposure to rodents and/or their fleas or contact with a known plague case.
- Patients must have a fever of at least 38 °C that developed rapidly, and have one of the following:
- One or more buboes (defined as tender lymph node swelling >=1 cm) that appeared after or at the same time as the fever; or
- Clinical suspicion of pneumonic plague (prostration, cough, increased respiratory rate, hemoptysis and/or purulent sputum); or
- Clinical suspicion of plague AND an epidemiological link with other cases.
- Only patients that are later confirmed by standard diagnostic tests will be included in the final analysis. Patients who do not have plague confirmed by standard tests will still be included in the safety analysis.
Who cannot join
- Has signs fitting plague meningitis (severely ill patient with signs of plague and one or more of the following: headache, fever, sensorial disturbances, neck and back stiffness, and/or positive Kernig and Brudzinski signs).
- Has hypotension unresponsive to fluid therapy (i.e. shock). In adults hypotension is defined as systolic blood pressure < 80 mmHg and heart rate > 110/min; in children it will need to be diagnosed by attending physician or medical officer.
- Has an "illness severity score" of 16 or higher (see Patient Record)
- Has a known allergy to gentamicin, streptomycin, or trimethoprim-sulfamethoxazole
- Is receiving dialysis for renal failure
- Has other severe underlying disease such as hepatic failure or other severe organ failure
- Has taken tetracyclines, quinolones, gentamicin, streptomycin, trimethoprim-sulfamethoxazole, or chloramphenicol in the last 24 hours. If the patient has taken medications that are not known, he/she will still be enrolled.
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Safety and Efficacy of Gentamicin Versus Streptomycin for the Treatment of Naturally Occurring Human Plague and Evaluation of Rapid Diagnostic Test Kits for Yersinia Pestis
This clinical trial will compare the effectiveness of streptomycin, which historically is the standard drug for treatment of plague, with gentamicin. The hypothesis is that gentamicin is not inferior to streptomycin but that it will have less severe side effects. The study is being done in Madagascar because that country reports the most plague cases in the world. Patients coming into a participating clinic with suspected plague (bubonic, pneumonic, or septicemic) will be randomized into one of two treatment arms after giving informed consent. Patients will be monitored for side effects and for improvement of symptoms.
In addition, rapid diagnostic test strips have been developed but not fully evaluated for use on humans. The investigators will evaluate these new tests on specimens from the same patients, comparing their performance with that of classical diagnostic methods such as culture and serology.
Read the detailed description
This protocol will guide clinical trials of treatment of naturally occurring human plague cases in African countries with a high incidence of human plague. The safety and efficacy of gentamicin will be compared to the standard drug regimen that is already used in Madagascar (streptomycin/co-trimoxazole) for treatment of plague. Data from this trial will be valuable to optimize clinical management of plague in many countries, including Madagascar and the United States.
In collaboration with the governments and health officials of Madagascar, the investigators will implement a randomized, controlled, non-blinded drug trial to compare the effectiveness and side effect profile of gentamicin to the national standard plague treatment.
Cases of plague will be identified through clinic-based surveillance in areas with a high incidence and/or in areas that have experienced outbreaks in recent years. After giving informed consent, patients will be randomly assigned to one of two treatment arms, each arm receiving a different antimicrobial. One patient group will be treated with gentamicin; the other group ("control group") will receive streptomycin alone or with co-trimoxazole.
This protocol will follow the national guideline of the Madagascar Ministry of Health, which means that patients with bubonic plague in the streptomycin treatment arm will receive streptomycin followed by trimethoprim-sulfamethoxazole. The only adaptation is that enrolled patients with renal insufficiency will receive adjusted dosing of streptomycin, whereas the national standard treatment does not call for dose adjustment in renal failure.
The investigators will also evaluate several newly available, rapid "dipstick" tests for the diagnosis of plague using serum, bubo aspirate, sputum, and urine specimens that will have already been collected from the patients enrolled in the drug trial. These rapid tests have been developed by several American companies and the Institut Pasteur in Madagascar, and have not been fully evaluated for use with human specimens. These results will be compared to standard diagnostic techniques. Such rapid diagnostic tests will be useful for plague diagnosis in developing nations and during bioterrorism events.
- Conditions
- Plague
- Being tested
- gentamicin, streptomycin
- Keywords
- bubonic plague, pneumonic plague, septicemic plague, Yersinia pestis, Pasteurella pestis
- Medical subject headings
- Plague
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
gentamicinDrug
streptomycinDrug
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival or death at 2 weeks
Secondary outcomes (3)
Time to defervescence during treatment
Number and severity of adverse effects at 2 weeks
Complications at 2 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted10 Aug 2005 (estimated)
- Study startAug 2004
- Study completionFeb 2007
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for PlagueStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2/3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 114 participants (actual)
Sponsor and investigators
- Lead sponsor
- Centers for Disease Control and Prevention
- Sponsor type
- US federal agency
- Collaborators
- Food and Drug Administration (FDA), Ministry of Health, Madagascar, Ministry of Health, Uganda
- Investigators
- Kevin Griffith, MD, MPH, Principal investigator, Centers for Disease Control and PreventionMartin Schriefer, PhD, Principal investigator, Centers for Disease Control and Prevention
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00128466
- Sponsor's protocol ID
- CDC-NCID-3700
- Status last verified
- Feb 2009
- First submitted
- 9 Aug 2005
- Last updated
- 26 Feb 2009
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 26 Feb 2009. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Gentamicin Versus Streptomycin for the Treatment of Naturally Occurring Human Plague and Evaluation of Rapid Diagnostic Test Kits for Yersinia Pestis
- ClinicalTrials.gov ID
- NCT00128466
- Acronym / sponsor ID
- CDC-NCID-3700
- Conditions
- Plague
- Keywords
- bubonic plague, pneumonic plague, septicemic plague, Yersinia pestis, Pasteurella pestis
- Phase
- Phase 2/3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 114 participants (actual)
- Lead sponsor
- Centers for Disease Control and PreventionUS federal agency
- Collaborators
- Food and Drug Administration (FDA), Ministry of Health, Madagascar, Ministry of Health, Uganda
- Study start
- Aug 2004
- Study completion
- Feb 2007 (actual)
- First posted
- 10 Aug 2005 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This clinical trial will compare the effectiveness of streptomycin, which historically is the standard drug for treatment of plague, with gentamicin. The hypothesis is that gentamicin is not inferior to streptomycin but that it will have less severe side effects. The study is being done in Madagascar because that country reports the most plague cases in the world. Patients coming into a participating clinic with suspected plague (bubonic, pneumonic, or septicemic) will be randomized into one of two treatment arms after giving informed consent. Patients will be monitored for side effects and for improvement of symptoms.
In addition, rapid diagnostic test strips have been developed but not fully evaluated for use on humans. The investigators will evaluate these new tests on specimens from the same patients, comparing their performance with that of classical diagnostic methods such as culture and serology.
Detailed description
This protocol will guide clinical trials of treatment of naturally occurring human plague cases in African countries with a high incidence of human plague. The safety and efficacy of gentamicin will be compared to the standard drug regimen that is already used in Madagascar (streptomycin/co-trimoxazole) for treatment of plague. Data from this trial will be valuable to optimize clinical management of plague in many countries, including Madagascar and the United States.
In collaboration with the governments and health officials of Madagascar, the investigators will implement a randomized, controlled, non-blinded drug trial to compare the effectiveness and side effect profile of gentamicin to the national standard plague treatment.
Cases of plague will be identified through clinic-based surveillance in areas with a high incidence and/or in areas that have experienced outbreaks in recent years. After giving informed consent, patients will be randomly assigned to one of two treatment arms, each arm receiving a different antimicrobial. One patient group will be treated with gentamicin; the other group ("control group") will receive streptomycin alone or with co-trimoxazole.
This protocol will follow the national guideline of the Madagascar Ministry of Health, which means that patients with bubonic plague in the streptomycin treatment arm will receive streptomycin followed by trimethoprim-sulfamethoxazole. The only adaptation is that enrolled patients with renal insufficiency will receive adjusted dosing of streptomycin, whereas the national standard treatment does not call for dose adjustment in renal failure.
The investigators will also evaluate several newly available, rapid "dipstick" tests for the diagnosis of plague using serum, bubo aspirate, sputum, and urine specimens that will have already been collected from the patients enrolled in the drug trial. These rapid tests have been developed by several American companies and the Institut Pasteur in Madagascar, and have not been fully evaluated for use with human specimens. These results will be compared to standard diagnostic techniques. Such rapid diagnostic tests will be useful for plague diagnosis in developing nations and during bioterrorism events.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
Who may qualify
- Ages
- 2 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- 2 years of age or older.
- Patients must have had potential exposure to rodents and/or their fleas or contact with a known plague case.
- Patients must have a fever of at least 38 °C that developed rapidly, and have one of the following:
- Only patients that are later confirmed by standard diagnostic tests will be included in the final analysis. Patients who do not have plague confirmed by standard tests will still be included in the safety analysis.
Key exclusion criteria (7 listed)
- Has signs fitting plague meningitis (severely ill patient with signs of plague and one or more of the following: headache, fever, sensorial disturbances, neck and back stiffness, and/or positive Kernig and Brudzinski signs).
- Has hypotension unresponsive to fluid therapy (i.e. shock). In adults hypotension is defined as systolic blood pressure < 80 mmHg and heart rate > 110/min; in children it will need to be diagnosed by attending physician or medical officer.
- Has an "illness severity score" of 16 or higher (see Patient Record)
- Has a known allergy to gentamicin, streptomycin, or trimethoprim-sulfamethoxazole
- Is receiving dialysis for renal failure
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| gentamicin | Drug | – |
| streptomycin | Drug | – |
Primary outcome
Survival or death at 2 weeks
3 secondary outcomes
Time to defervescence during treatment
Number and severity of adverse effects at 2 weeks
Complications at 2 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 26 Feb 2009.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Kevin Griffith, MD, MPH principal investigator
Centers for Disease Control and Prevention
Martin Schriefer, PhD principal investigator
Centers for Disease Control and Prevention
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2/3 study testing gentamicin and streptomycin in people with Plague, run by Centers for Disease Control and Prevention at 1 site in Madagascar.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 7 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 26 Feb 2009. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Madagascar. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this combined phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Survival or death at 2 weeks. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 26 Feb 2009.