Plague, BubonicPhase 3IMASOYNCT04110340
Ciprofloxacin Versus an Aminoglycoside Followed by Ciprofloxacin for Bubonic Plague
A Phase 3 study testing Ciprofloxacin, Streptomycin and Gentamicin in people with Plague, Bubonic and Plague, Pneumonic, run by University of Oxford at 1 site in Madagascar.
Trial summary
The primary objective of this trial is to test the hypothesis that ciprofloxacin monotherapy given (orally, intravenously, or combination) for 10 days is non-inferior to an aminoglycoside (given on days 1-3) followed by ciprofloxacin (given on days 4-10) in the treatment of bubonic plague. Read more about this study
- Who is it for?
- Any age
- Conditions the study is for
- Plague, Bubonic, Plague, Pneumonic
- What is being tested?
- Ciprofloxacin, Streptomycin and Gentamicin
- Type of treatment
- Pill or oral medicine, Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 222 participants
- Where
- 1 siteMadagascar
- Study dates
- 15 Feb 2020to 5 Feb 2025
- Phase
- Phase 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 Any age
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
None listed.
Who cannot join
- Known allergy to aminoglycosides or fluoroquinolones
- Tendinitis
- Myasthenia gravis
- Theophylline or warfarin use
- Already treated for bubonic or pneumonic plague in the preceeding 3 months
- Women who report being pregnant
- Inclusion of patients to the pneumonic plague observational cohort:
- Suspected, probable and confirmed cases of pneumonic plague
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Open-label, Randomised, Non-inferiority Trial of the Efficacy and Safety of Ciprofloxacin Versus an Aminoglycoside Followed by Ciprofloxacin in the Treatment of Bubonic Plague
The primary objective of this trial is to test the hypothesis that ciprofloxacin monotherapy given (orally, intravenously, or combination) for 10 days is non-inferior to an aminoglycoside (given on days 1-3) followed by ciprofloxacin (given on days 4-10) in the treatment of bubonic plague.
Secondary objectives are:
Read more
- to evaluate the level and kinetics of anti-Y. pestis antibodies of patients (bubonic and pneumonic plague) included in the study (anti-F1 ELISA techniques) at D1, D11, D21, M3 for patients who are positive at D21, and M12 for patients who are positive at M3.
The tertiary objectives are:
- to evaluate the level and kinetics of the levels of anti-Y. pestis antibodies and circulating F1 antigen of the patients (bubonic and pneumonic plague) included in the study (Luminex MagPix techniques with a Multiplex containing anti-F1 and rLcrV antigens and an F1 antigen capture multiplex) at D1, D11, D21, M3 for patients positive at D21, and M12 for patients who are positive at M3.
Observational non-comparative study of pneumonic plague
- The primary objective is to document the efficacy and safety of the currently recommended combination therapy treatment of pneumonic plague - an aminoglycoside (streptomycin or gentamicin) and ciprofloxacin combination therapy.
- The secondary and tertiary objectives of the bubonic plague trial also apply to the pneumonic plague cohort.
Read the detailed description
An individually randomised, open label, non-inferiority trial of ciprofloxacin versus an aminoglycoside and ciprofloxacin in patients with bubonic plague. We are using a non-inferiority design since the overall cure rate for bubonic plague without septicaemia with streptomycin is approximately 95%. As a result, demonstrating superiority would be unnecessary and impractical given the sample size that would be required. Our aim is therefore to demonstrate that ciprofloxacin alone is not more than 15% inferior to an aminoglycoside followed by ciprofloxacin. (15% is the non-inferiority margin in our study). We will recruit patients with a clinical suspicion of bubonic plague, but the size of our sample is powered based on an intention to treat infected patients sample size of 190, where infected is defined as a confirmed or probable case of bubonic plague. As a result the total number of patients to be enrolled will be higher than 190. We estimate that we will need to recruit approximately 600 patients with bubonic plague to achieve a sample size of 190 confirmed/probable bubonic plague patients. However, to mitigate risks of being under-powered we will propose to recruit for three full seasons with a minimum target of 190 confirmed/probable cases. Should we achieve the target of 190 confirmed/probable bubonic plague cases before the end of the final transmission season, we will nevertheless continue to recruit until the end of the season to retain power in the event of different treatment success percentages and to allow us to increase precision.
We will also recruit and collect data on patients with pneumonic plague, who will be enrolled in to a parallel observational cohort.
- Conditions
- Plague, Bubonic, Plague, Pneumonic
- Being tested
- Ciprofloxacin, Streptomycin, Gentamicin
- Medical subject headings
- Plague
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CiprofloxacinDrug
Adults: Ciprofloxacin 500mg orally twice daily (or 400mg IV twice daily for those who cannot take oral medication) for 10 days;
Children:Ciprofloxacin 15mg/kg twice daily (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take oral - maximum dose 400mg) for 10 days.
Patients who begin intravenous therapy may switch to oral administration once they are able to swallow or once deemed clinically appropriate by the treating physician.
StreptomycinDrug
Adults: streptomycin 1g twice daily for three days, followed by ciprofloxacin 500mg orally twice daily (or ciprofloxacin 400mg twice daily by IV for those unable to take orally) for an additional 7 days.
Children: streptomycin 15mg/kg twice daily for three days followed by ciprofloxacin 15mg/kg twice daily (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take oral - maximum dose 400mg) for 7 additional days.
Patients who begin intravenous therapy may switch to oral administration once they are able to swallow or once deemed clinically appropriate by the treating physician.
GentamicinDrug
Adults: 2.5mg/kg IV gentamicin twice daily for 3 days followed by ciprofloxacin 500 mg orally twice daily (or ciprofloxacin 400 mg twice daily IV for those who cannot take oral) for a further 7 days.
Children: 2.5mg/kg IV gentamicin twice daily for 3 days, followed by ciprofloxacin 15mg/kg (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take the oral route) for a further 7 days.
| Study group | Role | What they receive |
|---|---|---|
| Ciprofloxacin Arm | Active comparator | Adults: Ciprofloxacin 500mg orally twice daily (or 400mg IV twice daily for those who cannot take oral medication) for 10 days;
Children:Ciprofloxacin 15mg/kg twice daily (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take oral - maximum dose 400mg) for 10 days. Receives: Drug: Ciprofloxacin |
| Control arm | Other | Adults: streptomycin 1g twice daily for three days, followed by ciprofloxacin 500mg orally twice daily (or ciprofloxacin 400mg twice daily by IV for those who cannot take it orally) for an additional 7 days.
OR
2.5mg/kg IV gentamicin twice daily for 3 days followed by ciprofloxacin 500 mg orally twice daily (or ciprofloxacin 400 mg twice daily IV for those who cannot take oral) for a further 7 days.
Children: streptomycin 15mg/kg twice daily for three days followed by ciprofloxacin 15mg/kg twice daily (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take oral - maximum dose 400mg) for 7 additional days.
OR
2.5mg/kg IV gentamicin twice daily for 3 days, followed by ciprofloxacin 15mg/kg (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take the oral route) for a further 7 days. Receives: Drug: Ciprofloxacin; Drug: Streptomycin; Drug: Gentamicin |
What is being measured
The primary outcome is the main question the study is designed to answer.
Proportion of patients with bubonic plague with a therapeutic response (assessed on day 11).Therapeutic response is defined as follows for subjects with a visible bubo:
- Alive
- Absence of fever
- Has not received alternative treatment for plague
- No clinical decision to continue anti-plague antibiotics beyond day 10
Measured: 11 days
Secondary outcomes (17)
Bubonic plague
- Proportion of patients without fever (uncorrected axillary temperature <37.5C) at Day 4
Measured: 4 days
Bubonic plague
- Proportion of patients with a pain score < 3 at Day 4 (using pain scale questionnaires)
Measured: 4 days
Bubonic plague
- Proportion of patients with a pain score < 3 at Day 11 (using pain scale questionnaires)
Measured: 11 days
Bubonic plague
- Mean % change in bubo size at Day 4 (measured by use of calipers and/or ultrasound)
Measured: 4 days
Bubonic plague
- Mean % change in bubo size at Day11 (measured by use of calipers and/or ultrasound)
Measured: 11 days
Bubonic plague
- Proportion of patients experiencing a serious adverse event on or before Day 4
Measured: 4 days
Bubonic plague
- Proportion of patients experiencing a serious adverse event on or before Day 11
Measured: 11 days
Bubonic plague
- Proportion of patients experiencing a serious adverse event on or before Day 21
Measured: 21 days
Bubonic plague
- Proportion of patients who are fully adherent to the study treatment schedule.
Measured: 21 days
Pneumonic plague
Proportion of patients with a therapeutic response at Day 11. Therapeutic response is defined as follows:
- Alive
- Resolution of fever (uncorrected axillary temperature <37.5C)
- Resolution of tachypnoea (RR< 24 in adults, but age-specific in children)
Measured: 11 days
Pneumonic plague
- Proportion of patients without fever (uncorrected axillary temperature <37.5C) at Day 4
Measured: 4 days
Pneumonic plague
- Proportion of patients with tachypnoea resolution (RR< 24 in adults, but age-specific in children) at Day 4
Measured: 4 days
Pneumonic plague
- Proportion of patients experiencing a serious adverse event on or before Day 4
Measured: 4 days
Pneumonic plague
- Proportion of patients experiencing a serious adverse event on or before Day 11
Measured: 11 days
Pneumonic plague
- Proportion of patients experiencing a serious adverse event on or before Day 21
Measured: 21 days
Pneumonic plague
- Proportion of patients who are fully adherent to the study treatment schedule.
Measured: 21 days
Therapeutic response is defined as follows for subjects with a visible bubo:
- Alive AND
- Absence of fever at D11 AND
- At least a 25% decrease in bubo size (in the case of multiple buboes, the largest bubo) AND
- Has not received alternative treatment for plague AND
- No clinical decision to continue anti-plague antibiotics beyond day 10 ● Therapeutic response is defined as follows for subjects with small buboes that are palpable but not measurable:
- Alive AND
- Absence of fever at D11 AND
- Bubo has not enlarged AND
- Has not received alternative treatment for plague AND
- No clinical decision to continue anti-plague antibiotics beyond day 10
Measured: 11 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Oct 2019
- Study start15 Feb 2020
- Primary completion30 Apr 2024
- Study completion5 Feb 2025
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Plague, BubonicStudies of the same condition, open and under way.
- More trials run by University of OxfordThe sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Parallel groups
- Model description
- An open label, randomised, non-inferiority trial of the efficacy and safety of ciprofloxacin versus an aminoglycoside + ciprofloxacin in treatment of bubonic plague. We are using a non-inferiority design since the overall cure rate for bubonic plague without septicaemia with streptomycin is approximately 95%. As a result, demonstrating superiority would be unnecessary and impractical given the sample size that would be required. Our aim is therefore to demonstrate that ciprofloxacin alone is not more than 15% inferior to an aminoglycoside followed by ciprofloxacin.
- Masking
- None (open label)
- Enrolment
- 222 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Oxford
- Sponsor type
- University, hospital or other
- Collaborators
- Hôpital Universitaire Joseph Raseta Befelatanana CHU d'Antananarivo, Institut Pasteur de Madagascar, Foreign, Commonwealth and Development Office and Wellcome (216273.Z.19.Z)
- Responsible party
- Sponsor
- Investigators
- Peter W Horby, MD, Principal investigator, University of Oxford
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04110340
- Sponsor's protocol ID
- 45-18
- Acronym
- IMASOY
- Status last verified
- Feb 2025
- First submitted
- 28 Jan 2019
- Last updated
- 6 Mar 2025
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Anonymised data relating to the published analyses will be made available through an existing online repository (either at the University of Oxford or LSHTM) once the trial results are published.
Publications
Randremanana RV, Raberahona M, Bourner J, Rajerison M, Edwards T, Randriamparany R, Fehizoro Razafindratsinana T, Razananaivo LH, Zadonirina G, Mayouya-Gamana T, Salam APA, Mangahasimbola RT, Andrianaivoarimanana V, Pesonel E, Rakotoarivelo RA, Randria MJD, Horby P, Olliaro P; IMASOY Study Group. Ciprofloxacin versus Aminoglycoside-Ciprofloxacin for Bubonic Plague. N Engl J Med. 2025 Aug 7;393(6):544-555. doi: 10.1056/NEJMoa2413772.
PubMed 40768716Randremanana RV, Raberahona M, de Dieu Randria MJ, Bourner J, Zadonirina G, Razananaivo H, Mayouya-Gamana T, Mangahasimbola R, Pesonel E, Gillesen A, Rajerison M, Andrianaivoarimanana V, Edwards T, Horby P, Olliaro P. An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus an aminoglycoside + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial-an update to the published protocol. Trials. 2024 Jul 5;25(1):457. doi: 10.1186/s13063-024-08302-7.
PubMed 38970065Randremanana RV, Raberahona M, Randria MJD, Rajerison M, Andrianaivoarimanana V, Legrand A, Rasoanaivo TF, Randriamparany R, Mayouya-Gamana T, Mangahasimbola R, Bourner J, Salam A, Gillesen A, Edwards T, Schoenhals M, Baril L, Horby P, Olliaro P. An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus streptomycin + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial. Trials. 2020 Aug 17;21(1):722. doi: 10.1186/s13063-020-04642-2.
PubMed 32807214
Study at a glance
From the registry record, last updated by the sponsor on 6 Mar 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open-label, Randomised, Non-inferiority Trial of the Efficacy and Safety of Ciprofloxacin Versus an Aminoglycoside Followed by Ciprofloxacin in the Treatment of Bubonic Plague
- ClinicalTrials.gov ID
- NCT04110340
- Acronym / sponsor ID
- IMASOY / 45-18
- Conditions
- Plague, Bubonic, Plague, Pneumonic
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 222 participants (actual)
- Lead sponsor
- University of OxfordUniversity, hospital or other
- Collaborators
- Hôpital Universitaire Joseph Raseta Befelatanana CHU d'Antananarivo, Institut Pasteur de Madagascar, Foreign, Commonwealth and Development Office and Wellcome (216273.Z.19.Z)
- Study start
- 15 Feb 2020 (actual)
- Primary completion
- 30 Apr 2024 (actual)
- Study completion
- 5 Feb 2025 (actual)
- First posted
- 1 Oct 2019 (actual)
- 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.
The primary objective of this trial is to test the hypothesis that ciprofloxacin monotherapy given (orally, intravenously, or combination) for 10 days is non-inferior to an aminoglycoside (given on days 1-3) followed by ciprofloxacin (given on days 4-10) in the treatment of bubonic plague.
Secondary objectives are:
- to evaluate the level and kinetics of anti-Y. pestis antibodies of patients (bubonic and pneumonic plague) included in the study (anti-F1 ELISA techniques) at D1, D11, D21, M3 for patients who are positive at D21, and M12 for patients who are positive at M3.
The tertiary objectives are:
- to evaluate the level and kinetics of the levels of anti-Y. pestis antibodies and circulating F1 antigen of the patients (bubonic and pneumonic plague) included in the study (Luminex MagPix techniques with a Multiplex containing anti-F1 and rLcrV antigens and an F1 antigen capture multiplex) at D1, D11, D21, M3 for patients positive at D21, and M12 for patients who are positive at M3.
Observational non-comparative study of pneumonic plague
- The primary objective is to document the efficacy and safety of the currently recommended combination therapy treatment of pneumonic plague - an aminoglycoside (streptomycin or gentamicin) and ciprofloxacin combination therapy.
- The secondary and tertiary objectives of the bubonic plague trial also apply to the pneumonic plague cohort.
Detailed description
An individually randomised, open label, non-inferiority trial of ciprofloxacin versus an aminoglycoside and ciprofloxacin in patients with bubonic plague. We are using a non-inferiority design since the overall cure rate for bubonic plague without septicaemia with streptomycin is approximately 95%. As a result, demonstrating superiority would be unnecessary and impractical given the sample size that would be required. Our aim is therefore to demonstrate that ciprofloxacin alone is not more than 15% inferior to an aminoglycoside followed by ciprofloxacin. (15% is the non-inferiority margin in our study). We will recruit patients with a clinical suspicion of bubonic plague, but the size of our sample is powered based on an intention to treat infected patients sample size of 190, where infected is defined as a confirmed or probable case of bubonic plague. As a result the total number of patients to be enrolled will be higher than 190. We estimate that we will need to recruit approximately 600 patients with bubonic plague to achieve a sample size of 190 confirmed/probable bubonic plague patients. However, to mitigate risks of being under-powered we will propose to recruit for three full seasons with a minimum target of 190 confirmed/probable cases. Should we achieve the target of 190 confirmed/probable bubonic plague cases before the end of the final transmission season, we will nevertheless continue to recruit until the end of the season to retain power in the event of different treatment success percentages and to allow us to increase precision.
We will also recruit and collect data on patients with pneumonic plague, who will be enrolled in to a parallel observational cohort.
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- An open label, randomised, non-inferiority trial of the efficacy and safety of ciprofloxacin versus an aminoglycoside + ciprofloxacin in treatment of bubonic plague. We are using a non-inferiority design since the overall cure rate for bubonic plague without septicaemia with streptomycin is approximately 95%. As a result, demonstrating superiority would be unnecessary and impractical given the sample size that would be required. Our aim is therefore to demonstrate that ciprofloxacin alone is not more than 15% inferior to an aminoglycoside followed by ciprofloxacin.
| Arm | Type | Receives |
|---|---|---|
| Ciprofloxacin Arm | Active comparator | Drug: CiprofloxacinAdults: Ciprofloxacin 500mg orally twice daily (or 400mg IV twice daily for those who cannot take oral medication) for 10 days; Children:Ciprofloxacin 15mg/kg twice daily (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take oral - maximum dose 400mg) for 10 days. |
| Control arm | Other | Drug: Ciprofloxacin, Drug: Streptomycin, Drug: GentamicinAdults: streptomycin 1g twice daily for three days, followed by ciprofloxacin 500mg orally twice daily (or ciprofloxacin 400mg twice daily by IV for those who cannot take it orally) for an additional 7 days. OR 2.5mg/kg IV gentamicin twice daily for 3 days followed by ciprofloxacin 500 mg orally twice daily (or ciprofloxacin 400 mg twice daily IV for those who cannot take oral) for a further 7 days. Children: streptomycin 15mg/kg twice daily for three days followed by ciprofloxacin 15mg/kg twice daily (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take oral - maximum dose 400mg) for 7 additional days. OR 2.5mg/kg IV gentamicin twice daily for 3 days, followed by ciprofloxacin 15mg/kg (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take the oral route) for a further 7 days. |
Who may qualify
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (0 listed)
Key exclusion criteria (8 listed)
- Known allergy to aminoglycosides or fluoroquinolones
- Tendinitis
- Myasthenia gravis
- Theophylline or warfarin use
- Already treated for bubonic or pneumonic plague in the preceeding 3 months
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 |
|---|---|---|
| CiprofloxacinAdults: Ciprofloxacin 500mg orally twice daily (or 400mg IV twice daily for those who cannot take oral medication) for 10 days; Children:Ciprofloxacin 15mg/kg twice daily (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take oral - maximum dose 400mg) for 10 days. Patients who begin intravenous therapy may switch to oral administration once they are able to swallow or once deemed clinically appropriate by the treating physician. | Drug | Ciprofloxacin Arm, Control arm |
| StreptomycinAdults: streptomycin 1g twice daily for three days, followed by ciprofloxacin 500mg orally twice daily (or ciprofloxacin 400mg twice daily by IV for those unable to take orally) for an additional 7 days. Children: streptomycin 15mg/kg twice daily for three days followed by ciprofloxacin 15mg/kg twice daily (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take oral - maximum dose 400mg) for 7 additional days. Patients who begin intravenous therapy may switch to oral administration once they are able to swallow or once deemed clinically appropriate by the treating physician. | Drug | Control arm |
| GentamicinAdults: 2.5mg/kg IV gentamicin twice daily for 3 days followed by ciprofloxacin 500 mg orally twice daily (or ciprofloxacin 400 mg twice daily IV for those who cannot take oral) for a further 7 days. Children: 2.5mg/kg IV gentamicin twice daily for 3 days, followed by ciprofloxacin 15mg/kg (max 500mg per dose) orally (or 10mg/kg IV twice daily for those who cannot take the oral route) for a further 7 days. | Drug | Control arm |
Primary outcome
Proportion of patients with bubonic plague with a therapeutic response (assessed on day 11).Therapeutic response is defined as follows for subjects with a visible bubo:
Time frame: 11 days
* Alive * Absence of fever * Has not received alternative treatment for plague * No clinical decision to continue anti-plague antibiotics beyond day 10
17 secondary outcomes
Bubonic plague
Time frame: 4 days
Bubonic plague
Time frame: 4 days
Bubonic plague
Time frame: 11 days
Bubonic plague
Time frame: 4 days
Bubonic plague
Time frame: 11 days
Bubonic plague
Time frame: 4 days
Bubonic plague
Time frame: 11 days
Bubonic plague
Time frame: 21 days
Bubonic plague
Time frame: 21 days
Pneumonic plague
Time frame: 11 days
Pneumonic plague
Time frame: 4 days
Pneumonic plague
Time frame: 4 days
Pneumonic plague
Time frame: 4 days
Pneumonic plague
Time frame: 11 days
Pneumonic plague
Time frame: 21 days
Pneumonic plague
Time frame: 21 days
Therapeutic response is defined as follows for subjects with a visible bubo:
Time frame: 11 days
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 6 Mar 2025.
- Derived from this study: PubMed 40768716Randremanana RV, Raberahona M, Bourner J, Rajerison M, Edwards T, Randriamparany R, Fehizoro Razafindratsinana T, Razananaivo LH, Zadonirina G, Mayouya-Gamana T, Salam APA, Mangahasimbola RT, Andrianaivoarimanana V, Pesonel E, Rakotoarivelo RA, Randria MJD, Horby P, Olliaro P; IMASOY Study Group. Ciprofloxacin versus Aminoglycoside-Ciprofloxacin for Bubonic Plague. N Engl J Med. 2025 Aug 7;393(6):544-555. doi: 10.1056/NEJMoa2413772.
- Derived from this study: PubMed 38970065Randremanana RV, Raberahona M, de Dieu Randria MJ, Bourner J, Zadonirina G, Razananaivo H, Mayouya-Gamana T, Mangahasimbola R, Pesonel E, Gillesen A, Rajerison M, Andrianaivoarimanana V, Edwards T, Horby P, Olliaro P. An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus an aminoglycoside + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial-an update to the published protocol. Trials. 2024 Jul 5;25(1):457. doi: 10.1186/s13063-024-08302-7.
- Derived from this study: PubMed 32807214Randremanana RV, Raberahona M, Randria MJD, Rajerison M, Andrianaivoarimanana V, Legrand A, Rasoanaivo TF, Randriamparany R, Mayouya-Gamana T, Mangahasimbola R, Bourner J, Salam A, Gillesen A, Edwards T, Schoenhals M, Baril L, Horby P, Olliaro P. An open-label, randomized, non-inferiority trial of the efficacy and safety of ciprofloxacin versus streptomycin + ciprofloxacin in the treatment of bubonic plague (IMASOY): study protocol for a randomized control trial. Trials. 2020 Aug 17;21(1):722. doi: 10.1186/s13063-020-04642-2.
- Individual participant dataSharing planned: Yes. Anonymised data relating to the published analyses will be made available through an existing online repository (either at the University of Oxford or LSHTM) once the trial results are published.
Related trials for Plague, Bubonic
Not yet recruitingObservational study
Testing of a New Rapid Antigen Test for Plague in Ituri, Democratic Republic of the Congo.
Plague, Bubonic; Plague, Skin
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.
Peter W Horby, MD principal investigator
University of Oxford
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Ciprofloxacin, Streptomycin and Gentamicin in people with Plague, Bubonic and Plague, Pneumonic, run by University of Oxford 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 0 inclusion and 8 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 6 Mar 2025. 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 phase mean?
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?
Proportion of patients with bubonic plague with a therapeutic response (assessed on day 11).Therapeutic response is defined as follows for subjects with a visible bubo: (time frame: 11 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04110340, which also lists 3 linked publications.
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 6 Mar 2025.