Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT03224052 |
| Other study ID # |
MSHR 2016-2579 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
May 1, 2016 |
| Est. completion date |
January 1, 2018 |
Study information
| Verified date |
March 2024 |
| Source |
Menzies School of Health Research |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational
|
Clinical 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.
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.
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.
