A Randomized Double Blinded Comparison of Ceftazidime and Meropenem in Severe Melioidosis

NCT00579956 | Unknown DMC

• 1 other identifier: OXTREC 018-06
• Study Type: interventional
• Target: 750
• Locations: 1 country
• Sites: 2

Brief Summary

Melioidosis, an infection caused by the bacterium Burkholderia pseudomallei, is a major cause of community-acquired septicaemia in northeast Thailand. Common manifestations include cavitating pneumonia, hepatic and splenic abscesses, and soft tissue and joint infections. Despite improvements in diagnostic procedures and treatment, the mortality of severe melioidosis remains unacceptably high - approximately 35% with currently used antibiotics (ceftazidime or co-amoxiclav). There is clear evidence that antibiotics can affect mortality; the use of ceftazidime rather than previous regimens (doxycycline + chloramphenicol + co-trimoxazole) led to a 50% reduction in mortality from 80% to 35%. However, the mortality in the first 48 hours has not been altered by any treatment regimen. A key question is whether alternative antibiotics could improve early outcome. The hypothesis tested is that meropenem is superior to ceftazidime in terms of mortality for the treatment of melioidosis.

Conditions

Melioidosis

Outcome Measures

Primary Outcomes (1)

• All cause mortality

  In hospital

Secondary Outcomes (5)

• All cause mortality in patients culture positive for melioidosis

  In hospital

• Switch of antimicrobial therapy

  In hospital

• Adverse drug reactions

  1 month

• Fever clearance time (time to body temperature of less than 37.5°C for at least 48 hours)

  In hospital

• Length of hospital stay

  months

Study Arms (2)

Meropenem

EXPERIMENTAL

Meropenem

Drug: Meropenem

Ceftazidime

ACTIVE COMPARATOR

Ceftazidime

Drug: Ceftazidime

Interventions

Meropenem DRUG

Meropenem 1gm, diluted with 50ml normal saline solution IV every 8 hours for at least 10 days. The dose will be adjusted according to the creatinine clearance.

Meropenem

Ceftazidime DRUG

Ceftazidime 120mg/kg/day divided into 3 equal doses (maximum dose 2 gram/dose), diluted with 50ml normal saline solution IV every 8 hours for at least 10 days The dose will be adjusted according to the plasma creatinine level

Ceftazidime

Eligibility Criteria

• Age: 15 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• A. Community acquired sepsis, and melioidosis is suspected:
• Suspected melioidosis (12): all of the following are defined as 'clinically probable' melioidosis
• A history of frequent contact with soil or surface water in the endemic area
• At least one of the following risk factors: diabetes mellitus, chronic renal failure or renal calculi, thalassaemia, aplastic anaemia or steroid abuse
• An illness compatible with melioidosis, including the presence of sepsis, acute pneumonia, acute pyelonephritis, septic arthritis, parotid disease or skin or soft tissue infection, or
• An evidence of intra-abdominal suppuration (hepatic or splenic abscesses) regardless of risk factors or exposure history
• Sepsis: defined as patients who have Systemic Inflammatory Response Syndrome (SIRS) - two or more of the following, clinically ascribed to infection:
• Fever: temperature \>38°C or \<36°C
• Tachycardia: heart rate \>90 beats/min
• Tachypnoea:
• Respiratory rate \>20 breaths/minute; or
• PaCO2 \<32 mmHg; or
• Mechanical ventilation
• White cell count \>12,000 cells/mL or \<4,000 cells/mL or \>10% band forms B. Age \> 14 years. C. Need hospitalisation and intravenous antibiotic administration. D. Willingness to participate in the study and written, informed consent obtained from the patient.

You may not qualify if:

• A. Pregnant or lactating women. B. Known hypersensitivity to meropenem or ceftazidime. C. Previous isolate with known resistance to ceftazidime or meropenem. D. Patients not expected to remain in hospital for treatment. E. Patients with community-acquired sepsis with cultures positive for other organisms.
• F. Patients treated with antibiotics active against B. pseudomallei (including ceftazidime, amoxicillin-clavulanate, meropenem) for this episode for greater than 24 hours.

Sponsors & Collaborators

• University of Oxford: lead
• Mahidol University: collaborator
• Wellcome Trust: collaborator

Study Sites (2)

Sappasithiprasong Hospital

Ubonratchathani, Changwat Ubon Ratchathani, Thailand

RECRUITING

Udon Thani General Hospital

Udon Thani, Thailand

RECRUITING

Related Publications (1)

• Foong YC, Tan M, Bradbury RS. Melioidosis: a review. Rural Remote Health. 2014;14(4):2763. Epub 2014 Oct 30.

  PMID: 25359677 DERIVED

MeSH Terms

Conditions

Melioidosis

Interventions

Meropenem; Ceftazidime

Condition Hierarchy (Ancestors)

Burkholderia Infections; Gram-Negative Bacterial Infections; Bacterial Infections; Bacterial Infections and Mycoses; Infections

Intervention Hierarchy (Ancestors)

Thienamycins; Carbapenems; beta-Lactams; Lactams; Amides; Organic Chemicals; Heterocyclic Compounds, 2-Ring; Heterocyclic Compounds, Fused-Ring; Heterocyclic Compounds; Cephaloridine; Cephalosporins; Thiazines; Sulfur Compounds

Study Officials

• Wirongrong Chierakul, MD

  Mahidol University

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Wirongrong Chierakul, MD

CONTACT

6689 1058571; kae@tropmedres.ac

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER

Study Record Dates

• First Submitted: December 18, 2007
• First Posted: December 24, 2007
• Study Start: December 1, 2007
• Primary Completion: September 1, 2010
• Study Completion: September 1, 2010
• Last Updated: June 4, 2008

Record last verified: 2007-08

Locations

TH (2)