Antimicrobial Drug ResistanceDYNAMITENCT06258551
Dynamics of Colonization and Infection by Multidrug-Resistant Pathogens in Immunocompromised and Critically Ill Patients
An observational study of Antimicrobial Drug Resistance and Antibiotic Resistant Infection, run by The Methodist Hospital Research Institute at 2 sites in United States.
Trial summary
The goal of this observational study is to investigate how bacterial populations from the intestine and mouth of patients change during the hospitalization period and evaluate if some populations of specific bacteria increase or decrease the risk of acquiring an infection or becoming colonized by pathogenic bacteria. Read more about this study
- Who is it for?
- Ages 18 years and olderHealthy volunteers can take part
- Conditions the study is for
- Antimicrobial Drug Resistance, Antibiotic Resistant Infection, Clostridium Difficile
- How many people
- 1,000 participants
- Where
- 2 sitesUnited States
- Study dates
- 8 Dec 2020to Jun 2026
- 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 18 years and older
- All sexes
- Healthy volunteers accepted
- Adult, Older adult
Study population: Patients are recruited from the intensive care units and stem cell transplant units from two major metropolitan hospitals
Who may be able to join
- Admission to an intensive care unit or stem cell transplant unit (for allogeneic stem cell transplantation) within previous 24 hours
Who cannot join
- <18 years of age
- Pregnancy
- History of inflammatory bowel disease (Crohn's disease, ulcerative colitis)
- Gastrointestinal derivation (colostomy, ileostomy, etc.)
Trial locations and contacts
2 sites in 1 country.
United States2 sites, 2 recruiting
- Recruiting
Houston Methodist Hospital
Houston, Texas, 77030
Cesar A Arias, MD, PhD, Msc, 346-238-4870, caarias@houstonmethodist.org
Andrea M deTranaltes, 713-569-4258, amdetranaltes@houstonmethodist.org
- Recruiting
The University of Texas MD Anderson Cancer Center
Houston, Texas, 77030
Samuel Shelburne, MD, PhD, 713-792-3280, SShelburne@mdanderson.org
About this study
The goal of this observational study is to investigate how bacterial populations from the intestine and mouth of patients change during the hospitalization period and evaluate if some populations of specific bacteria increase or decrease the risk of acquiring an infection or becoming colonized by pathogenic bacteria. Participants will have the following samples collected during enrollment: stool samples (maximum 2x/week), blood draws (1x/week), oral swab (1x/week).
Read the detailed description
The objectives of this study are to dissect the main microbial, clinical, and antimicrobial resistance determinants that impact colonization and infection by vancomycin-resistant enterococci (VRE), extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Clostridium difficile; to evaluate the role of commensal microbiota in VRE, ESBL-E/CRE, and C. difficile colonization, and to define the functional aspects of keystone microbiota and mechanisms of protection against colonization/infection.
Patients will be recruited from both intensive care units (n=500) and stem cell transplant units (n=500) and will be followed until discharge from these units, or for a maximum of four weeks. In addition to stool, blood, and oral samples, enrolled patients will have clinical data collected by chart review to evaluate colonization/infection-related clinical status, microbiological laboratory information, exposure to antibiotics, and clinical outcomes. Positive clinical cultures taken during the course of hospitalization will also be collected for analysis.
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 |
|---|---|---|
| Intensive Care Unit | Patients admitted to an intensive care unit (No interventions administered) | |
| Bone Marrow Transplant Unit | Patients admitted to a cancer treatment center for allogeneic stem cell transplantation (No interventions administered) |
What is being measured
The primary outcome is the main question the study is designed to answer.
Impact of Colonization on Clinical Outcomes Using DOOR Analysis
A desirability of outcome ranking (DOOR) algorithm will be used to analyze the impact of colonization by any target organism (CRE/ESBL-E, VRE, or C. difficile) on 30 day clinical outcomes. DOOR outcomes will be ranked as follows: 1) alive without infection, 2) alive with infection, or 3) dead.
Measured: 30 days
Secondary outcomes (1)
Additional Clinical Predictors of Negative Outcomes
Separate univariable logistic regression models will be used to evaluate associations between each individual component of the DOOR outcome (i.e., mortality and clinical infection) and the type of colonization as well as other independent predictors of mortality (e.g., neutropenia, hemodialysis, Pitt score, among others). Variables with p < 0.10 in bivariate analysis will also be included in the logistic models to assess for independent associations with outcome.
Measured: 30 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted14 Feb 2024
- Study start8 Dec 2020
- Primary completionJun 2026 (estimated)
- Study completionJun 2026 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (7)Papers the sponsor has linked to this study.
- Other trials for Antimicrobial Drug ResistanceStudies of the same condition, open and under way.
- More trials run by The Methodist Hospital Research InstituteThe sponsor's other registered studies.
- 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
- 1,000 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Methodist Hospital Research Institute
- Sponsor type
- University, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), M.D. Anderson Cancer Center, Baylor College of Medicine, University of Houston, William Marsh Rice University, The University of Texas Health Science Center, Houston
- Responsible party
- Principal investigator, Cesar Arias, The Methodist Hospital Research Institute
- Investigators
- Cesar A Arias, MD, PhD, Msc, Principal investigator, The Methodist Hospital Research Institute
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT06258551
- Sponsor's protocol ID
- PRO00035528
- Other IDs
- 1P01AI152999-01
- Acronym
- DYNAMITE
- Status last verified
- Feb 2024
- First submitted
- 6 Feb 2024
- Last updated
- 14 Feb 2024
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data generated by the DYNAMITE projects and Functional Genomics Core will be made available to the public through presentations at scientific meetings, peer-reviewed journal publications and articles, and/or direct sharing or deposit of data into publicly accessible databases. All banked bacterial specimens (both infecting and colonizing isolates) will be made available. Single bacterial whole genome sequencing data will be submitted to the Short Read Archive (SRA) at NCBI for unassembled data, as well as GenBank for assembled data.16S and shotgun metagenomic data will be submitted to the SRA following host sequence removal, and assembled 16S amplicons will be submitted to GenBank. Proteomic raw MS data will be submitted to the Proteomics Identifications (PRIDE) Archive. Metabolomics raw MS data will be submitted to the National Metabolomics Data Repository (NMDR). All custom bioinformatics pipelines, tools, and analytical scripts will be made available in a GitHub repository.
Publications
Evans SR, Rubin D, Follmann D, Pennello G, Huskins WC, Powers JH, Schoenfeld D, Chuang-Stein C, Cosgrove SE, Fowler VG Jr, Lautenbach E, Chambers HF. Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR). Clin Infect Dis. 2015 Sep 1;61(5):800-6. doi: 10.1093/cid/civ495. Epub 2015 Jun 25.
PubMed 26113652van Duin D, Lok JJ, Earley M, Cober E, Richter SS, Perez F, Salata RA, Kalayjian RC, Watkins RR, Doi Y, Kaye KS, Fowler VG Jr, Paterson DL, Bonomo RA, Evans S; Antibacterial Resistance Leadership Group. Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae. Clin Infect Dis. 2018 Jan 6;66(2):163-171. doi: 10.1093/cid/cix783.
PubMed 29020404Taur Y, Xavier JB, Lipuma L, Ubeda C, Goldberg J, Gobourne A, Lee YJ, Dubin KA, Socci ND, Viale A, Perales MA, Jenq RR, van den Brink MR, Pamer EG. Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. 2012 Oct;55(7):905-14. doi: 10.1093/cid/cis580. Epub 2012 Jun 20.
PubMed 22718773Satlin MJ, Chavda KD, Baker TM, Chen L, Shashkina E, Soave R, Small CB, Jacobs SE, Shore TB, van Besien K, Westblade LF, Schuetz AN, Fowler VG Jr, Jenkins SG, Walsh TJ, Kreiswirth BN. Colonization With Levofloxacin-resistant Extended-spectrum beta-Lactamase-producing Enterobacteriaceae and Risk of Bacteremia in Hematopoietic Stem Cell Transplant Recipients. Clin Infect Dis. 2018 Nov 13;67(11):1720-1728. doi: 10.1093/cid/ciy363.
PubMed 29701766Caballero S, Carter R, Ke X, Susac B, Leiner IM, Kim GJ, Miller L, Ling L, Manova K, Pamer EG. Distinct but Spatially Overlapping Intestinal Niches for Vancomycin-Resistant Enterococcus faecium and Carbapenem-Resistant Klebsiella pneumoniae. PLoS Pathog. 2015 Sep 3;11(9):e1005132. doi: 10.1371/journal.ppat.1005132. eCollection 2015 Sep.
PubMed 26334306Lee KH, Han SH, Yong D, Paik HC, Lee JG, Kim MS, Joo DJ, Choi JS, Kim SI, Kim YS, Park MS, Kim SY, Yoon YN, Kang S, Jeong SJ, Choi JY, Song YG, Kim JM. Acquisition of Carbapenemase-Producing Enterobacteriaceae in Solid Organ Transplantation Recipients. Transplant Proc. 2018 Dec;50(10):3748-3755. doi: 10.1016/j.transproceed.2018.01.058.
PubMed 30577266Ulrich RJ, Santhosh K, Mogle JA, Young VB, Rao K. Is Clostridium difficile infection a risk factor for subsequent bloodstream infection? Anaerobe. 2017 Dec;48:27-33. doi: 10.1016/j.anaerobe.2017.06.020. Epub 2017 Jun 29.
PubMed 28669864
Study at a glance
From the registry record, last updated by the sponsor on 14 Feb 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dynamics of Colonization and Infection by Multidrug-Resistant Pathogens in Immunocompromised and Critically Ill Patients
- ClinicalTrials.gov ID
- NCT06258551
- Acronym / sponsor ID
- DYNAMITE / PRO00035528
- Conditions
- Antimicrobial Drug Resistance, Antibiotic Resistant Infection, Clostridium Difficile, Carbapenem-Resistant Enterobacteriaceae Infection, Extended Spectrum Beta-Lactamase Producing Bacteria Infection, Vancomycin Resistant Enterococci Infection
- Study type
- Observational
- Recruitment status
- Unknown status
- Enrolment
- 1,000 participants (estimated)
- Lead sponsor
- The Methodist Hospital Research InstituteUniversity, hospital or other
- Collaborators
- National Institute of Allergy and Infectious Diseases (NIAID), M.D. Anderson Cancer Center, Baylor College of Medicine, University of Houston, William Marsh Rice University, The University of Texas Health Science Center, Houston
- Study start
- 8 Dec 2020 (actual)
- Primary completion
- Jun 2026 (estimated)
- Study completion
- Jun 2026 (estimated)
- First posted
- 14 Feb 2024 (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.
The goal of this observational study is to investigate how bacterial populations from the intestine and mouth of patients change during the hospitalization period and evaluate if some populations of specific bacteria increase or decrease the risk of acquiring an infection or becoming colonized by pathogenic bacteria. Participants will have the following samples collected during enrollment: stool samples (maximum 2x/week), blood draws (1x/week), oral swab (1x/week).
Detailed description
The objectives of this study are to dissect the main microbial, clinical, and antimicrobial resistance determinants that impact colonization and infection by vancomycin-resistant enterococci (VRE), extended-spectrum beta-lactamase producing Enterobacterales (ESBL-E), carbapenem-resistant Enterobacterales (CRE), and Clostridium difficile; to evaluate the role of commensal microbiota in VRE, ESBL-E/CRE, and C. difficile colonization, and to define the functional aspects of keystone microbiota and mechanisms of protection against colonization/infection.
Patients will be recruited from both intensive care units (n=500) and stem cell transplant units (n=500) and will be followed until discharge from these units, or for a maximum of four weeks. In addition to stool, blood, and oral samples, enrolled patients will have clinical data collected by chart review to evaluate colonization/infection-related clinical status, microbiological laboratory information, exposure to antibiotics, and clinical outcomes. Positive clinical cultures taken during the course of hospitalization will also be collected for analysis.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Intensive Care Unit | – | –Patients admitted to an intensive care unit (No interventions administered) |
| Bone Marrow Transplant Unit | – | –Patients admitted to a cancer treatment center for allogeneic stem cell transplantation (No interventions administered) |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult, Older adult
- Study population
- Patients are recruited from the intensive care units and stem cell transplant units from two major metropolitan hospitals
Key inclusion criteria (1 listed)
- Admission to an intensive care unit or stem cell transplant unit (for allogeneic stem cell transplantation) within previous 24 hours
Key exclusion criteria (4 listed)
- <18 years of age
- Pregnancy
- History of inflammatory bowel disease (Crohn's disease, ulcerative colitis)
- Gastrointestinal derivation (colostomy, ileostomy, etc.)
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
Impact of Colonization on Clinical Outcomes Using DOOR Analysis
Time frame: 30 days
A desirability of outcome ranking (DOOR) algorithm will be used to analyze the impact of colonization by any target organism (CRE/ESBL-E, VRE, or C. difficile) on 30 day clinical outcomes. DOOR outcomes will be ranked as follows: 1) alive without infection, 2) alive with infection, or 3) dead.
1 secondary outcome
Additional Clinical Predictors of Negative Outcomes
Time frame: 30 days
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 14 Feb 2024.
- Background: PubMed 26113652Evans SR, Rubin D, Follmann D, Pennello G, Huskins WC, Powers JH, Schoenfeld D, Chuang-Stein C, Cosgrove SE, Fowler VG Jr, Lautenbach E, Chambers HF. Desirability of Outcome Ranking (DOOR) and Response Adjusted for Duration of Antibiotic Risk (RADAR). Clin Infect Dis. 2015 Sep 1;61(5):800-6. doi: 10.1093/cid/civ495. Epub 2015 Jun 25.
- Background: PubMed 29020404van Duin D, Lok JJ, Earley M, Cober E, Richter SS, Perez F, Salata RA, Kalayjian RC, Watkins RR, Doi Y, Kaye KS, Fowler VG Jr, Paterson DL, Bonomo RA, Evans S; Antibacterial Resistance Leadership Group. Colistin Versus Ceftazidime-Avibactam in the Treatment of Infections Due to Carbapenem-Resistant Enterobacteriaceae. Clin Infect Dis. 2018 Jan 6;66(2):163-171. doi: 10.1093/cid/cix783.
- Background: PubMed 22718773Taur Y, Xavier JB, Lipuma L, Ubeda C, Goldberg J, Gobourne A, Lee YJ, Dubin KA, Socci ND, Viale A, Perales MA, Jenq RR, van den Brink MR, Pamer EG. Intestinal domination and the risk of bacteremia in patients undergoing allogeneic hematopoietic stem cell transplantation. Clin Infect Dis. 2012 Oct;55(7):905-14. doi: 10.1093/cid/cis580. Epub 2012 Jun 20.
- Background: PubMed 29701766Satlin MJ, Chavda KD, Baker TM, Chen L, Shashkina E, Soave R, Small CB, Jacobs SE, Shore TB, van Besien K, Westblade LF, Schuetz AN, Fowler VG Jr, Jenkins SG, Walsh TJ, Kreiswirth BN. Colonization With Levofloxacin-resistant Extended-spectrum beta-Lactamase-producing Enterobacteriaceae and Risk of Bacteremia in Hematopoietic Stem Cell Transplant Recipients. Clin Infect Dis. 2018 Nov 13;67(11):1720-1728. doi: 10.1093/cid/ciy363.
- Background: PubMed 26334306Caballero S, Carter R, Ke X, Susac B, Leiner IM, Kim GJ, Miller L, Ling L, Manova K, Pamer EG. Distinct but Spatially Overlapping Intestinal Niches for Vancomycin-Resistant Enterococcus faecium and Carbapenem-Resistant Klebsiella pneumoniae. PLoS Pathog. 2015 Sep 3;11(9):e1005132. doi: 10.1371/journal.ppat.1005132. eCollection 2015 Sep.
- Background: PubMed 30577266Lee KH, Han SH, Yong D, Paik HC, Lee JG, Kim MS, Joo DJ, Choi JS, Kim SI, Kim YS, Park MS, Kim SY, Yoon YN, Kang S, Jeong SJ, Choi JY, Song YG, Kim JM. Acquisition of Carbapenemase-Producing Enterobacteriaceae in Solid Organ Transplantation Recipients. Transplant Proc. 2018 Dec;50(10):3748-3755. doi: 10.1016/j.transproceed.2018.01.058.
- Background: PubMed 28669864Ulrich RJ, Santhosh K, Mogle JA, Young VB, Rao K. Is Clostridium difficile infection a risk factor for subsequent bloodstream infection? Anaerobe. 2017 Dec;48:27-33. doi: 10.1016/j.anaerobe.2017.06.020. Epub 2017 Jun 29.
- Centers for Disease Control and Prevention Antimicrobial Resistance Threats ReportLink provided by the sponsor.
- World Health Organization Antimicrobial Resistance Fact SheetLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Data generated by the DYNAMITE projects and Functional Genomics Core will be made available to the public through presentations at scientific meetings, peer-reviewed journal publications and articles, and/or direct sharing or deposit of data into publicly accessible databases. All banked bacterial specimens (both infecting and colonizing isolates) will be made available. Single bacterial whole genome sequencing data will be submitted to the Short Read Archive (SRA) at NCBI for unassembled data, as well as GenBank for assembled data.16S and shotgun metagenomic data will be submitted to the SRA following host sequence removal, and assembled 16S amplicons will be submitted to GenBank. Proteomic raw MS data will be submitted to the Proteomics Identifications (PRIDE) Archive. Metabolomics raw MS data will be submitted to the National Metabolomics Data Repository (NMDR). All custom bioinformatics pipelines, tools, and analytical scripts will be made available in a GitHub repository.
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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.
Cesar A Arias, MD, PhD, Msc principal investigator
The Methodist Hospital Research Institute
2 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Antimicrobial Drug Resistance and Antibiotic Resistant Infection, run by The Methodist Hospital Research Institute at 2 sites in United States.
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 1 inclusion and 4 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: status not confirmed, as of the sponsor's last update on 14 Feb 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 sites in United States. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Cesar A Arias, MD, PhD, Msc (346-238-4870, CAArias@Houstonmethodist.org), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Impact of Colonization on Clinical Outcomes Using DOOR Analysis (time frame: 30 days). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT06258551, which also lists 7 linked publications.
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 14 Feb 2024.