MALDITOF Versus Routine Clinical Microbiology for Identifying Pathogens; a Randomized Diagnostic Trial (MALDITOF)

• ClinicalTrials.gov Identifier: NCT02306330
• Recruitment Status: Completed
• First Posted: December 3, 2014
• Last Update Posted: November 15, 2016
• Sponsor: Oxford University Clinical Research Unit, Vietnam
• Collaborators: National Hospital for Tropical Diseases, Hanoi, Vietnam; Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam
• Information provided by (Responsible Party): Oxford University Clinical Research Unit, Vietnam

Study Description

Brief Summary:

MALDI-TOF MS is capable of directly identifying bacteria and fungi in positive blood cultures, which may be beneficial to patient management. Therefore, MALDI-TOF MS is an important new technology that is becoming routine in developed countries. It is currently unknown whether MALDITOF MS improves diagnostics, costs and patient outcomes in developing countries. This study will assess the clinical impact of a MALDITOF MS system (Maldi Biotyper, Bruker, Germany) in the resource constrained setting of Vietnam and at what cost.

Condition or disease	Intervention/treatment	Phase
Bacterial Infections; Fungal Infections	Device: Malditof; Other: Routine clinical microbiology	Not Applicable

Detailed Description:

When an eligible specimen from a patient shows pathogen growth, the pathogen identification will be randomized to either MaldiTof or routine diagnostics ('diagnostic pipelines'). Randomization to MaldiTof or routine diagnostics will be 1:1 with stratification by hospital and specimen type (blood vs. other). Isolates grown from all eligible specimens of the same patient will be assigned to the same diagnostic pipeline as the first randomized specimen of that patient.

Allocation to diagnostic arm will be assigned by a web based randomization program. When a pathogen is isolated from a positive eligible specimen, the laboratory technician will log onto the secure randomization program and enter the patient and specimen code. The random diagnostic pipeline allocation will then be generated, informed to the laboratory technician and logged in the study database. In the case of multiple specimens with pathogen growth for a single patient, the unique patient code will trigger the randomization program to generate the same diagnostic arm allocation as the previous sample(s).

Study Design

• Study Type: Interventional (Clinical Trial)
• Actual Enrollment: 802 participants
• Allocation: Randomized
• Intervention Model: Parallel Assignment
• Masking: Single (Outcomes Assessor)
• Primary Purpose: Diagnostic
• Official Title: Assessing Time to Reporting and Clinical Management of Patients With Severe Bacterial and Fungal Infections Between Two Diagnostic Approaches: Matrix-assisted Laser Desorption Ionization-time of Flight Mass Spectrometry Versus Routine Clinical Microbiology for Identifying Pathogens; a Randomized Diagnostic Trial
• Study Start Date: December 2014
• Actual Primary Completion Date: January 2016
• Actual Study Completion Date: January 2016

Arms and Interventions

Arm	Intervention/treatment
Experimental: Malditof; Specimens of patients (diagnostic aspirates from normally sterile sites: cerebrospinal fluid (CSF), deep abscesses, joint fluid, peritoneal fluid, and pleural fluid, deep tissue biopsies) in Malditof arm will be performed by Malditof instrument to identify the pathogens. It takes 20 minutes for Malditof to identify the pathogens. Then patients will be treated based on these results.	Device: Malditof; Malditof MS system is applied for Malditof group for identifying pathogens. It takes 20 minutes to give the results.
Active Comparator: Routine clinical microbiology; Specimens of patients (diagnostic aspirates from normally sterile sites: cerebrospinal fluid (CSF), deep abscesses, joint fluid, peritoneal fluid, and pleural fluid, deep tissue biopsies) in routine clinical microbiology arm will be conducted by the routine clinical microbiologies and followed the treatment process of the hospital.	Other: Routine clinical microbiology; Pathogens will be identified by the routine clinical microbiology of the hospital.

Outcome Measures

Primary Outcome Measures :

1. Proportion of patients on optimal antibiotic treatment [ Time Frame: Within 24 hours of positive culture (first growth of an eligible specimen). ]
   Optimal antibiotic treatment is defined as an antibiotic treatment for at least 48 hours since positive culture, targeted to the identified pathogen and later found to cover the organisms antimicrobial resistance profile, while avoiding unnecessary broad spectrum antibiotics (e.g. avoid carbapenems or multiple agents where other agents or single agents would provide sufficient coverage). This study aims to determine The proportion of patients on optimal antibiotic treatment within 24 hours of positive culture (first growth of an eligible specimen).

Secondary Outcome Measures :

1. The total duration of antibiotic treatment [ Time Frame: During treatment course, estimated to be 7-10 days. ]
2. The total number of antibiotic switches [ Time Frame: During treatment course, estimated to be 7-10 days. ]
3. Length of ICU stay [ Time Frame: During ICU admission, estimated to be 7 days ]
4. Length of hospital stay [ Time Frame: During hospital admission, estimated to be 12 days ]
5. Patient outcome: death, palliative discharge, survived with sequelae, recovered [ Time Frame: On or before discharge, estimated to be at 12 days ]
6. Costs of microbiological testing [ Time Frame: On or before discharge, estimated to be at 12 days ]
7. Treatment and hospital costs [ Time Frame: On or before discharge, estimated to be at 12 days ]

Other Outcome Measures:

1. Time from first growth of an eligible specimen to optimal antibiotic treatment. [ Time Frame: During hospital admission, estimated to be 0-48 hours ]
2. Time from specimen collection of positive eligible specimen to optimal antibiotic treatment [ Time Frame: During hospital admission, estimated to be 0-48 hours ]
3. The time from first recognition of isolate growth to issue of pathogen identification report [ Time Frame: Estimated 0-12 hours ]
4. The time from specimen collection to issue of pathogen identification report [ Time Frame: Estimated 24-48 hours ]
5. Time from first specimen collection to discharge [ Time Frame: Estimated to be 12 days ]
6. Time from first pathogen identification to discharge [ Time Frame: Estimated to be 10 days ]

Eligibility Criteria

• Ages Eligible for Study: Child, Adult, Older Adult
• Sexes Eligible for Study: All
• Accepts Healthy Volunteers: No

Criteria

Inclusion Criteria: Pathogen isolates from the following specimens: blood or diagnostic aspirates from normally sterile sites (including cerebrospinal fluid (CSF), deep abscesses, joint fluid, peritoneal fluid, and pleural fluid, deep tissue biopsies).

Exclusion Criteria:

• Specimens negative for all pathogens
• Specimens from sputum, respiratory or non-surgical wound swabs, nails, mucosal or skin biopsies, urine, fluid from drains, skin swabs and any others not listed in the inclusion criteria.

Contacts and Locations

Locations

Vietnam

National Hospital for Tropical Diseases

Ha Noi, Vietnam

Hospital for Tropical Diseases

Ho CHi Minh City, Vietnam

Sponsors and Collaborators

Oxford University Clinical Research Unit, Vietnam

National Hospital for Tropical Diseases, Hanoi, Vietnam

Hospital for Tropical Diseases, Ho Chi Minh City, Vietnam

Investigators

• Principal Investigator: Heiman Wertheim, MD, PhD; Oxford University of Clinical Research

More Information

Additional Information:

Oxford University Clinical Research Unit Viet Nam 

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):

Nadjm B, Dat VQ, Campbell JI, Dung VTV, Torre A, Tu NTC, Van NTT, Trinh DT, Lan NPH, Trung NV, Hang NTT, Hoi LT, Baker S, Wolbers M, Chau NVV, Van Kinh N, Thwaites GE, van Doorn HR, Wertheim HFL. A randomised controlled trial of matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDITOF-MS) versus conventional microbiological methods for identifying pathogens: Impact on optimal antimicrobial therapy of invasive bacterial and fungal infections in Vietnam. J Infect. 2019 Jun;78(6):454-460. doi: 10.1016/j.jinf.2019.03.010. Epub 2019 Mar 23.

• Responsible Party: Oxford University Clinical Research Unit, Vietnam
• ClinicalTrials.gov Identifier: NCT02306330
• Other Study ID Numbers: 09HN
• First Posted: December 3, 2014
• Last Update Posted: November 15, 2016
• Last Verified: December 2014

Keywords provided by Oxford University Clinical Research Unit, Vietnam:

Malditof; Malditof MS; matrix-assisted laser desorption ionization-time; identifying pathogens; randomized diagnostic trial

Additional relevant MeSH terms:

Infections; Communicable Diseases; Bacterial Infections; Mycoses; Disease Attributes; Pathologic Processes; Bacterial Infections and Mycoses