MalariaANTHEMNCT03224052
Empirical ANtibiotic THErapy in Adults Hospitalised With Malaria
An observational study of Malaria and Bacteremia, run by Menzies School of Health Research at 1 site in Burma.
Trial summary
While World Health Organization (WHO) guidelines recommend empirical antibacterial therapy as the standard of care in all African children with severe falciparum malaria, there are fewer data to guide the management of adults with the disease in low transmission settings. Read more about this study
- Who is it for?
- Ages 16 years and older
- Conditions the study is for
- Malaria, Bacteremia, Sepsis
- How many people
- 20 participants
- Where
- 1 siteBurma
- Study dates
- 1 May 2016to 1 Jan 2018
- Phase
- Observational
- 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 16 years and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Adults hospitalized with malaria at the four study sites
Who may be able to join
- Admitted to hospital
- Positive film for asexual forms Plasmodium falciparum or Plasmodium vivax or positive Rapid Diagnostic Test for either pathogen if blood film not immediately available (with confirmation on blood film as soon as possible).
- Informed consent
Who cannot join
- Age less than 16
- Pregnancy
- Patient's family declines consent
Trial locations and contacts
1 site in 1 country.
About this study
Official title: An Observational Trial of Empirical Antibiotic Therapy in Adults Hospitalised With Malaria
While World Health Organization (WHO) guidelines recommend empirical antibacterial therapy as the standard of care in all African children with severe falciparum malaria, there are fewer data to guide the management of adults with the disease in low transmission settings.
Presently WHO guidelines do not recommend empirical antibacterial therapy in adults with malaria in low transmission settings, instead antibacterial therapy is only clearly recommended in those patients in whom a serious bacterial co-infection is clinically suspected. However, in a pilot study in Myanmar (High Frequency of Clinically Significant Bacteremia in Adults Hospitalized With Falciparum Malaria PMID: 26989752) we found that 13% of adults hospitalized with falciparum malaria were bacteremic, with bacterial co-infection suspected by clinicians in the minority. Patients with serious bacterial infection are commonly not bacteraemic and so this probably underestimates the frequency of significant bacterial co-infection.
Read more
In that pilot study, over 75% of patients received empirical antibacterial therapy on admission to hospital, which would not accord with published WHO guidelines as clinicians suspected bacterial co-infection in only 17%. However, the study's 100% survival rate - when over half of the patients were at high risk of death - suggests that the administration of antibacterial therapy may be appropriate until bacterial co-infection is excluded.
There is also academic debate about the role of co-morbidities in the presentation of patients severely ill with vivax malaria. Bacterial co-infection has been reported in some - but by no means all - studies of severe vivax infection. It would be useful to determine the relative contribution of bacterial co-infection to the clinical presentation of patients with vivax malaria.
By systematically seeking evidence of bacterial co-infection in all patients hospitalized at the study sites, this study aims to determine if the bacterial infection is really as prevalent as was the case in the pilot study. Accordingly it aims to determine the utility of a strategy that includes empirical antibacterial therapy in adults hospitalized with malaria in low transmission settings, until significant bactrila infection has been excluded.
Read the detailed description
The study's participants will be adults hospitalized with malaria at four tertiary referral hospitals in Myanmar. The study will be a collaboration between clinicians at Insein General Hospital North Okkalapa General Hospital and Thingangyun General Hospital in Yangon and Naypyidaw General Hospital in Naypyidaw, Myanmar and the Department of Global Health at Menzies School of Health Research.
The study's participants will be cared for by local doctors and nurses according to current WHO guidelines for the management of severe malaria. Management will include a systematic screen for bacterial infection with a detailed history, examination, radiological and laboratory studies, including the collection of blood cultures in all patients (this is recommended in WHO guidelines, but rarely performed in the resource poor setting). The only difference to the current WHO guidelines for the management of severe malaria will be the administration of empirical antibacterial therapy to all participants with falciparum malaria on admission. Participants with vivax malaria - who have a much lower incidence of complicated disease - would be managed according to the existing WHO guidelines, which suggest that antibacterial therapy should only be commenced in the presence of convincing evidence of severe bacterial co-infection.
After informed consent is obtained, artesunate is administered and a detailed work up for bacterial co-infection is performed, all participants with falciparum malaria will receive empiric levofloxacin. This will continue until 48 hours when, if the patient is improving and the work up for infection is negative, antibiotics will be ceased. Conversely if cultures are positive, targeted antibacterial therapy will be commenced as soon as sensitivity data are available. In the setting of convincing clinical evidence of bacterial infection when cultures are negative (a patient with a chest x-ray consistent with pneumonia but in whom cultures are negative for example), appropriate antibacterial will be continued. Participants who deteriorate in the first 48 hours will have their antibacterial therapy escalated to vancomycin and meropenem (based on microbiological findings in our pilot study).
Participants hospitalized with vivax malaria will also receive parenteral antimalarial therapy and have a detailed work up for infection, but empirical antibacterial therapy will not be commenced. Study clinicians may start antibacterial therapy in the setting of positive cultures or unequivocal evidence of bacterial infection if cultures are negative.
The subsequent clinical course of the participants and the frequency of confirmed bacterial co-infection would be compared to historical controls at the study sites to determine the utility of empirical antibacterial therapy in adults hospitalized with malaria in Myanmar. These data would be generalizable to other low transmission settings potentially.
The plan is to continue the study for 3 years; we expect that this will allow sufficient time to enrol enough patients to answer the study questions. The data will be analysed annually by independent safety monitors (from the University of Medicine 2, Myanmar and The Kirby Institute, Australia) and the study terminated if clear benefit or harm is identified. Independent safety monitors will also follow the study locally, review all deaths and be available to address any concerns of the participants and their families.
- Conditions
- Malaria, Bacteremia, Sepsis
- Keywords
- Anti-Bacterial Agents, Falciparum, Vivax
- Medical subject headings
- Malaria, Bacteremia, Sepsis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
| Study group | Role | What they receive |
|---|---|---|
| Patients with falciparum malaria | Empirical antibiotic therapy with levofloxacin 750mg daily for 48 hours. This will be ceased if there is no laboratory or radiological evidence of infection at 48 hours.Therapy will be modified based on culture results or clinical judgment if cultures are not available. If patients deteriorate in the first 48 hours on levofloxacin, antibacterial therapy comprising vancomycin (1.5g bd) and meropenem (1g tds) will be substituted for levofloxacin in addition to increasing supportive care as appropriate. The dosing of all antibiotics will be adjusted according to creatinine clearance. | |
| Patients with vivax malaria | No empirical therapy will be commenced in these patients. If there is laboratory or radiological evidence of infection antibacterial therapy will be administered based on culture results or clinical judgment if cultures are not available. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Survival
Death before discharge from hospitalization
Measured: Within 30 days of enrolment
Secondary outcomes (1)
Supportive care requirement
A requirement for supportive care as determined by the attending clinician. Supportive care is defined as a requirement renal replacement therapy (clinical symptoms of acute renal failure), vasopressor support (mean arterial blood pressure of less than 65mmHg despite fluid resuscitation), blood transfusion (haemoglobin < 7 g/dL) or mechanical ventilation (due to type 1 or type 2 respiratory failure)
Measured: Within 30 days of enrolment
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Jul 2017
- Study start1 May 2016
- Primary completion31 Oct 2017
- Study completion1 Jan 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for MalariaStudies 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Menzies School of Health Research
- Sponsor type
- University, hospital or other
- Collaborators
- University of Medicine 2, Yangon
- Responsible party
- Sponsor
- Investigators
- Mar Mar Kyi, MD, Study director, University of Medicine 2, Yangon, Myanmar
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03224052
- Sponsor's protocol ID
- MSHR 2016-2579
- Acronym
- ANTHEM
- Status last verified
- Mar 2024
- First submitted
- 26 May 2016
- Last updated
- 15 Mar 2024
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Yes: The data will be stored for a period of five years after any resulting publication. Researchers who apply and receive approval from the Human Research Ethics Committees of the Menzies School of Health Research and the University of Medicine 2, Yangon will be able to review the data.
Study at a glance
From the registry record, last updated by the sponsor on 15 Mar 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Observational Trial of Empirical Antibiotic Therapy in Adults Hospitalised With Malaria
- ClinicalTrials.gov ID
- NCT03224052
- Acronym / sponsor ID
- ANTHEM / MSHR 2016-2579
- Conditions
- Malaria, Bacteremia, Sepsis
- Keywords
- Anti-Bacterial Agents, Falciparum, Vivax
- Study type
- Observational
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Menzies School of Health ResearchUniversity, hospital or other
- Collaborators
- University of Medicine 2, Yangon
- Study start
- 1 May 2016 (actual)
- Primary completion
- 31 Oct 2017 (actual)
- Study completion
- 1 Jan 2018 (actual)
- First posted
- 21 Jul 2017 (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.
While World Health Organization (WHO) guidelines recommend empirical antibacterial therapy as the standard of care in all African children with severe falciparum malaria, there are fewer data to guide the management of adults with the disease in low transmission settings.
Presently WHO guidelines do not recommend empirical antibacterial therapy in adults with malaria in low transmission settings, instead antibacterial therapy is only clearly recommended in those patients in whom a serious bacterial co-infection is clinically suspected. However, in a pilot study in Myanmar (High Frequency of Clinically Significant Bacteremia in Adults Hospitalized With Falciparum Malaria PMID: 26989752) we found that 13% of adults hospitalized with falciparum malaria were bacteremic, with bacterial co-infection suspected by clinicians in the minority. Patients with serious bacterial infection are commonly not bacteraemic and so this probably underestimates the frequency of significant bacterial co-infection.
In that pilot study, over 75% of patients received empirical antibacterial therapy on admission to hospital, which would not accord with published WHO guidelines as clinicians suspected bacterial co-infection in only 17%. However, the study's 100% survival rate - when over half of the patients were at high risk of death - suggests that the administration of antibacterial therapy may be appropriate until bacterial co-infection is excluded.
There is also academic debate about the role of co-morbidities in the presentation of patients severely ill with vivax malaria. Bacterial co-infection has been reported in some - but by no means all - studies of severe vivax infection. It would be useful to determine the relative contribution of bacterial co-infection to the clinical presentation of patients with vivax malaria.
By systematically seeking evidence of bacterial co-infection in all patients hospitalized at the study sites, this study aims to determine if the bacterial infection is really as prevalent as was the case in the pilot study. Accordingly it aims to determine the utility of a strategy that includes empirical antibacterial therapy in adults hospitalized with malaria in low transmission settings, until significant bactrila infection has been excluded.
Detailed description
The study's participants will be adults hospitalized with malaria at four tertiary referral hospitals in Myanmar. The study will be a collaboration between clinicians at Insein General Hospital North Okkalapa General Hospital and Thingangyun General Hospital in Yangon and Naypyidaw General Hospital in Naypyidaw, Myanmar and the Department of Global Health at Menzies School of Health Research.
The study's participants will be cared for by local doctors and nurses according to current WHO guidelines for the management of severe malaria. Management will include a systematic screen for bacterial infection with a detailed history, examination, radiological and laboratory studies, including the collection of blood cultures in all patients (this is recommended in WHO guidelines, but rarely performed in the resource poor setting). The only difference to the current WHO guidelines for the management of severe malaria will be the administration of empirical antibacterial therapy to all participants with falciparum malaria on admission. Participants with vivax malaria - who have a much lower incidence of complicated disease - would be managed according to the existing WHO guidelines, which suggest that antibacterial therapy should only be commenced in the presence of convincing evidence of severe bacterial co-infection.
After informed consent is obtained, artesunate is administered and a detailed work up for bacterial co-infection is performed, all participants with falciparum malaria will receive empiric levofloxacin. This will continue until 48 hours when, if the patient is improving and the work up for infection is negative, antibiotics will be ceased. Conversely if cultures are positive, targeted antibacterial therapy will be commenced as soon as sensitivity data are available. In the setting of convincing clinical evidence of bacterial infection when cultures are negative (a patient with a chest x-ray consistent with pneumonia but in whom cultures are negative for example), appropriate antibacterial will be continued. Participants who deteriorate in the first 48 hours will have their antibacterial therapy escalated to vancomycin and meropenem (based on microbiological findings in our pilot study).
Participants hospitalized with vivax malaria will also receive parenteral antimalarial therapy and have a detailed work up for infection, but empirical antibacterial therapy will not be commenced. Study clinicians may start antibacterial therapy in the setting of positive cultures or unequivocal evidence of bacterial infection if cultures are negative.
The subsequent clinical course of the participants and the frequency of confirmed bacterial co-infection would be compared to historical controls at the study sites to determine the utility of empirical antibacterial therapy in adults hospitalized with malaria in Myanmar. These data would be generalizable to other low transmission settings potentially.
The plan is to continue the study for 3 years; we expect that this will allow sufficient time to enrol enough patients to answer the study questions. The data will be analysed annually by independent safety monitors (from the University of Medicine 2, Myanmar and The Kirby Institute, Australia) and the study terminated if clear benefit or harm is identified. Independent safety monitors will also follow the study locally, review all deaths and be available to address any concerns of the participants and their families.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Patients with falciparum malaria | – | –Empirical antibiotic therapy with levofloxacin 750mg daily for 48 hours. This will be ceased if there is no laboratory or radiological evidence of infection at 48 hours.Therapy will be modified based on culture results or clinical judgment if cultures are not available. If patients deteriorate in the first 48 hours on levofloxacin, antibacterial therapy comprising vancomycin (1.5g bd) and meropenem (1g tds) will be substituted for levofloxacin in addition to increasing supportive care as appropriate. The dosing of all antibiotics will be adjusted according to creatinine clearance. |
| Patients with vivax malaria | – | –No empirical therapy will be commenced in these patients. If there is laboratory or radiological evidence of infection antibacterial therapy will be administered based on culture results or clinical judgment if cultures are not available. |
Who may qualify
- Ages
- 16 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Adults hospitalized with malaria at the four study sites
Key inclusion criteria (3 listed)
- Admitted to hospital
- Positive film for asexual forms Plasmodium falciparum or Plasmodium vivax or positive Rapid Diagnostic Test for either pathogen if blood film not immediately available (with confirmation on blood film as soon as possible).
- Informed consent
Key exclusion criteria (3 listed)
- Age less than 16
- Pregnancy
- Patient's family declines consent
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Primary outcome
Survival
Time frame: Within 30 days of enrolment
Death before discharge from hospitalization
1 secondary outcome
Supportive care requirement
Time frame: Within 30 days of enrolment
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 15 Mar 2024.
- Individual participant dataSharing planned: Yes. The data will be stored for a period of five years after any resulting publication. Researchers who apply and receive approval from the Human Research Ethics Committees of the Menzies School of Health Research and the University of Medicine 2, Yangon will be able to review the data.
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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.
Mar Mar Kyi, MD study director
University of Medicine 2, Yangon, Myanmar
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Malaria and Bacteremia, run by Menzies School of Health Research at 1 site in Burma.
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 3 inclusion and 3 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 15 Mar 2024. 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 Burma. 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.
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 (time frame: Within 30 days of enrolment). 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 15 Mar 2024.