Empirical ANtibiotic THErapy in Adults Hospitalised With Malaria

NCT03224052 | Completed DMC

• 1 other identifier: MSHR 2016-2579
• Study Type: observational
• Target: 20
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Malaria; Bacteremia; Sepsis

Keywords

Anti-Bacterial Agents; Falciparum; Vivax

Outcome Measures

Primary Outcomes (1)

• Survival

  Death before discharge from hospitalization

  Within 30 days of enrolment

Secondary Outcomes (1)

• Supportive care requirement

  Within 30 days of enrolment

Study Arms (2)

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.

Eligibility Criteria

• Age: 16 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Adults hospitalized with malaria at the four study sites

You may qualify if:

• 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

You may not qualify if:

• Age less than 16
• Pregnancy
• Patient's family declines consent

Sponsors & Collaborators

• Menzies School of Health Research: lead
• University of Medicine 2, Yangon: collaborator

Study Sites (1)

Insein General Hospital

Yangon, Burma

Location

Biospecimen

Retention: SAMPLES WITH DNA

Blood will be stored for analysis of K13 mutations in the Plasmodium falciparum specimens. Urine will be also be stored for analysis of glycocalyx break down products.

MeSH Terms

Conditions

Malaria; Bacteremia; Sepsis

Condition Hierarchy (Ancestors)

Protozoan Infections; Parasitic Diseases; Infections; Mosquito-Borne Diseases; Vector Borne Diseases; Bacterial Infections; Bacterial Infections and Mycoses; Systemic Inflammatory Response Syndrome; Inflammation; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Study Officials

• Mar Mar Kyi, MD

  University of Medicine 2, Yangon, Myanmar

  STUDY DIRECTOR

Study Design

• Study Type: observational
• Observational Model: COHORT
• Time Perspective: PROSPECTIVE
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 26, 2016
• First Posted: July 21, 2017
• Study Start: May 1, 2016
• Primary Completion: October 31, 2017
• Study Completion: January 1, 2018
• Last Updated: March 15, 2024

Record last verified: 2024-03

Data Sharing

• IPD Sharing: Will share
• Shared Documents: STUDY PROTOCOL, CSR
• Time Frame: The data will be available from October 2016 for 5 years.
• Access Criteria: 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.

Locations

BU (1)