The Agency for Healthcare Research and Quality (AHRQ) published a new Toolkit for Decolonization of Non-ICU Patients With Devices to help clinical teams implement a protocol to reduce bloodstream infections by approximately 30% in patients with specific medical devices.
The new toolkit is based on intervention materials successfully used in the ABATE Infection trial, one of the first NIH Collaboratory Trials of the NIH Pragmatic Trials Collaboratory. ABATE Infection was a large-scale pragmatic trial involving approximately 189,000 patients in the baseline period and 340,000 patients in the intervention period across 194 non–critical care units in 53 hospitals.
From the AHRQ announcement:
The free, customizable toolkit includes step-by-step instructions, handouts, and educational videos to show frontline teams how to apply a decolonization protocol for non-ICU patients who may be at greater risk of bloodstream infections because they have certain devices, such as central venous catheters. The decolonization protocol includes instructions on helping patients bathe with an antiseptic soap and applying a nasal antibiotic ointment to carriers of Methicillin-resistant Staphylococcus aureus (MRSA).
ABATE Infection was supported within the NIH Pragmatic Trials Collaboratory by a cooperative agreement from the National Institute of Allergy and Infectious Diseases and by the NIH Common Fund through a cooperative agreement from the Office of Strategic Coordination within the Office of the NIH Director. Learn more about ABATE Infection.
In 2012, the NIH Common Fund established the NIH Health Care Systems Research Collaboratory. The goal of the program is to improve the way clinical trials are conducted by creating an infrastructure for collaborative research with healthcare systems. The NIH Collaboratory launched with a Coordinating Center, Core Working Groups, and NIH Collaboratory Trials to conduct embedded pragmatic clinical trials (ePCTs) in partnership with healthcare system leaders and to work collaboratively with the NIH to solve problems as they arise, develop best practices, and share lessons and resources to with others conducting ePCTs.
Collaboratory Mission: Strengthen the national capacity to implement cost-effective large-scale research studies that engage healthcare delivery organizations as research partners.
With the first round of NIH Collaboratory Trials nearing completion, the project teams are beginning to publish results and share lessons with other researchers. We asked the principal investigators of the most recently completed projects to share insights about the important contributions of their studies.
Congratulations on finishing your NIH Collaboratory Trial: What do you think is the most important contribution of your study?
ABATE was conducted to determine whether routine bathing and showering with chlorhexidine soap would reduce multidrug-resistant organisms and bloodstream infections compared with usual care. The trial was conducted in 53 HCA Healthcare hospitals (194 non–critical care units)and included 340,000 patients in the intervention period.
“We found that there was no overall benefit to universal antiseptic bathing in non–intensive care units (ICUs). This is in stark contrast to the huge benefit demonstrated in ICUs in the REDUCE-MRSA trial, and may reflect the fact that non–critical care patients stay only a few days in the hospital and are less likely to develop infection. Nevertheless, we did find that antiseptic bathing and nasal decolonization reduced bloodstream infections and antibiotic-resistant organisms by over 30% in patients with devices outside of the ICU. This is important because they are 10% of the non-ICU population, but responsible for over half of bloodstream infections. They provide a valuable targeted population who appear to benefit from this intervention.”
LIRE was conducted to test the effectiveness of a simple and inexpensive intervention: inserting epidemiologic benchmarks into lumbar spine imaging reports. The goal of the trial was to reduce subsequent tests and treatments, including cross-sectional imaging (such as magnetic resonance imaging and computed tomography), opioid prescriptions, spinal injections, or surgery.
“I think that one of the most important contributions of the LIRE trial was demonstrating the feasibility of randomizing hundreds of thousands of patients to receive or not receive an intervention that we inserted into the radiology report. Before our trial began, there was a fair amount of skepticism about whether radiologists would accept routinely inserting prevalence information into their reports on a wide scale. We showed without a doubt that it was feasible.”
PPACT was designed to assess the potential benefit of helping patients adopt self-management skills for chronic pain, limit use of opioid medications, and identify factors amenable to treatment in the primary care setting in three Kaiser Permanente (Northwest, Georgia, and Hawaii) involving approximately 800 patients.
“We started a trial when everybody was still uncertain about what the trade-offs between external validity (and real-world issues that are important for implementation) and the rigor of internal validity. I don’t know if we got that right. There was an assumption that the trial needed to be cluster randomized, and I think it’s informative that only 1 of the 11 NIH-DOD-VA Pain Management Collaboratory trials was cluster randomized. We needed to be able to incubate, have embedded teams stay over time, and really shift the culture. Patients needed to get used to the idea of non-pharmacotherapy over several months, and we may have had more success if we had individually randomized our cohort. I learned a lot in this process.”
PROVEN was designed to evaluate the effectiveness of advance care planning video tools in the nursing home setting by partnering with 2 large healthcare systems that operate 492 nursing homes nationwide.
“PROVEN found an ACP Video Program did not significantly impact hospital transfers, burdensome treatments, or hospice enrollment among nursing home residents with advanced illness, however intervention fidelity was low. Nonetheless, PROVEN was one of the first large pragmatic trials conducted in US nursing homes. Thus, I feel its greatest contribution was setting a foundation of knowledge for the field in terms of methodologies that enable pragmatic trials in this setting and challenges to overcome.”
STOP CRC was conducted to determine whether EHR-embedded tools and clinic staff training in how to implement a mailed fecal immunochemical test (FIT) outreach program could increase colorectal cancer screening uptake among patients with historically lower CRC screening rates and worse CRC outcomes, such as those with low income, or who are on Medicaid or underinsured. STOP CRC was conducted in 26 Federally Qualified Health Centers (FQHCs) in Oregon and California and involved approximately 41,000 patients.
“The ability to work with FQHCs and their new electronic data systems was an important contribution. FQHC settings are not organized healthcare systems, such as Kaiser Permanente, where research is more routine. I think we contributed to the success of this type of research and enabled the FHQCs’ ability to do more of it.” — Dr. Beverly Green
“Our study designed real-time electronic health record tools to allow clinics to mail cancer screening tests to adults who were overdue. We learned a lot about the challenges clinics faced in implementing the program. We shared our learnings with hundreds of additional community clinics in Washington, Oregon, California to help them anticipate and overcome these challenges.”— Dr. Gloria Coronado
TiME was conducted to determine whether treatment with hemodialysis sessions that are longer than many patients in the United States currently receive reduces the high rate of mortality among people being treated with thrice-weekly maintenance hemodialysis. The trial was conducted in 2 large US dialysis provider organizations, DaVita, Inc. and Fresenius Medical Care – North America, and included 266 outpatient dialysis facilities with 7035 patients.
“TiME established a model for conducting real-world research for a group of patients for whom there is very little clinical trial data. Many of the approaches and lessons from TiME are now being applied to a new set of pragmatic trials in dialysis that are being conducted in the US and internationally. In my view, TiME’s greatest contribution was to create a foundation for ongoing efficient and rigorous evidence generation in dialysis.”
Data and resources from the NIH Collaboratory Trials are posted on the NIH Collaboratory’s Data and Resource Sharing page in the coming months. As part of the program’s commitment to sharing, all NIH Collaboratory Trials are expected to share data and resources, such as protocols, consent documents, public use datasets, computable phenotypes, and analytic code.
NIH Collaboratory researchers in 2019 continued to generate new knowledge and research methods in pragmatic clinical trials. Their work included insights from the Coordinating Center and Core Working Groups, large-scale analyses of data from the NIH Collaboratory Distributed Research Network, and results and innovative methodological approaches from the NIH Collaboratory Trials.
So far this year, the NIH Collaboratory has produced nearly 3 dozen articles in the peer-reviewed literature, including the primary results of the ABATE Infection trial, confirmation by the TiME trial of the feasibility of embedding large pragmatic trials in clinical care, and more:
The Active Bathing to Eliminate (ABATE) Infection trial compared routine bathing to decolonization with universal chlorhexidine and targeted nasal mupirocin in non-critical-care units. Similar interventions have been found to reduce multidrug-resistant pathogens and bloodstream infections in intensive care units (ICUs), and this was the first large-scale trial in non-critical-care units. The primary outcome was methicillin-resistant Staphylococcus aureus (MRSA) or vancomycin-resistant enterococcus (VRE) clinical cultures attributed to participating units.
“We found that universal decolonization did not reduce infection in the overall population, but in post-hoc analyses of patients with medical devices the regimen was associated with significant reductions in all-cause bloodstream infections and MRSA or VRE clinical cultures.” —Huang et al. The Lancet 2019
The ABATE Infection trial was a large-scale pragmatic trial involving approximately189,000 patients in the baseline period and 340,000 patients in the intervention period across 194 non-critical-care units in 53 hospitals. The trial was one of the first NIH Collaboratory Trials, and in keeping with the Collaboratory’s mission, the investigators have helped expand the knowledge base about the design, conduct, and dissemination of pragmatic clinical trials.
The Active Bathing to Eliminate (ABATE) Infection trial (ClinicalTrials.gov #NCT02063867) has completed its intervention phase—the first NIH Health Care Systems Research Collaboratory UH3 NIH Collaboratory Trial to reach this major milestone. The large-scale, cluster-randomized pragmatic clinical trial (PCT) was designed to assess an approach for reducing multidrug-resistant organisms and hospital-associated infections (HAIs) in nearly 200 non-critical care hospital units affiliated with Hospital Corporation of America (HCA) across the United States.
ABATE study PI Dr. Susan Huang
The ABATE study is led by principal investigator Dr. Susan Huang of the University of California, Irvine, who stated “We are elated to reach the successful completion of the trial thanks to an incredible investigative team at HCA, Harvard Pilgrim Health Care, Rush University, the University of Massachusetts Amherst, and UC Irvine. We look forward to what the trial data will tell us and hope that we can continue to find effective ways to protect patients from infection.”
In the ABATE study, patients hospitalized in non-critical care units were bathed either according to the hospital unit’s usual care procedures (the control group) or bathed with the topical antibacterial agent chlorhexidine (plus nasal administration of the antibiotic mupirocin for those patients who were colonized or infected with, or had a history of methicillin-resistant Staphylococcus aureus [MRSA] [the intervention group]). The study investigators will compare the number of unit-attributable, multidrug-resistant organisms in clinical cultures between the study arms; these organisms include vancomycin-resistant enterococci (VRE), MRSA, and gram-negative bacteria. In addition, the investigators will compare the number of unit-attributable infections in the bloodstream and urinary tract (all pathogens) and Clostridium difficile infections. Cultures were collected at baseline and post intervention and will be assessed to determine whether resistance emerged to decolonization products.
“We are elated to reach the successful completion of the trial thanks to an incredible investigative team at HCA, Harvard Pilgrim Health Care, Rush University, the University of Massachusetts Amherst, and UC Irvine.We look forward to what the trial data will tell us and hope that we can continue to find effective ways to protect patients from infection.”
Healthcare-associated infections caused by common bacteria, including MRSA and VRE, are a leading cause of preventable illness and death in the United States and are associated with upward of $6.5 billion in annual healthcare costs. Although these bacteria normally live on the skin or in the nose, under certain circumstances they can cause serious or even life-threatening infections. Hospitalized patients who are ill or who have weakened immune systems are especially at risk for such infections. Because these pathogens are resistant to many antibiotics, they can be difficult to treat.
In intensive care units (ICUs), reducing the amount of such bacteria (a process referred to as decolonization) by treating patients’ skin with chlorhexidine and their noses with mupirocin ointment has been shown to reduce MRSA infections and all-cause bacteremias. However, relatively little is known about the effects of decolonization in hospital settings outside of critical care units, although this is where the majority of such infections occur. The ABATE trial, in contrast, is testing its bathing and decolonization strategy in adult medical, surgical, oncology, and step-down units (pediatric, psychology, peri-partum, and bone marrow transplantation units were excluded).
Over the course of the study, more than a million showers and baths were taken, and all sites have completed the intervention. The next steps for the ABATE investigators are to finish strain collection over the coming weeks, and then clean, validate, and analyze the data over the coming months.
Huang SS, Septimus E, Moody J, et al. Randomized Evaluation of Decolonization vs. Universal Clearance to Eliminate Methicillin-Resistant Staphylococcus aureus in ICUs (REDUCE MRSA Trial). 2012. Available at: https://idsa.confex.com/idsa/2012/webprogram/Paper36049.html. Accessed December 15, 1024.
Huang SS, Septimus E, Kleinman K, et al. Targeted versus universal decolonization to prevent ICU infection. N Engl J Med 2013;368:2255–2265. PMID: 23718152. doi: 10.1056/NEJMoa1207290.
A new article published in the journal Trials provides a look at how the Pragmatic–Explanatory Continuum Indicator Summary, or PRECIS, rating system can be applied to clinical trials designs in order to examine where a given study sits on the spectrum of explanatory versus pragmatic clinical trials.
The PRECIS-2 criteria are used to rate study designs as more or less “pragmatic” according to multiple domains that include participant eligibility, recruitment methods, setting, organization, analysis methods, primary outcomes, and more. In this context, “pragmatic” refers to trials that are designed to study a therapy or intervention in a “real world” setting similar or identical to the one in which the therapy will actually be used. Pragmatic trials stand in contrast to explanatory trials, which are typically designed to demonstrate the safety and efficacy of an intervention under highly controlled conditions and in carefully selected groups of participants, but which may also be difficult to generalize to larger or more varied populations.
PRECIS-2 Wheel. Kirsty Loudon et al. BMJ 2015;350:bmj.h2147. Copyright 2015 by British Medical Journal Publishing Group. Used by permission.
Clinical trials are almost never wholly “explanatory” or wholly “pragmatic.” Instead, many studies exist somewhere on a spectrum between these two categories. However, understanding how these different attributes apply to trials can help researchers design studies that are optimally fit for purpose, whether that purpose is to describe a biological mechanism (as in an explanatory trial) or to show how effective an intervention is when used across a broad population of patients (as in a pragmatic trial).
In their article in Trials, authors Karin Johnson, Gila Neta, and colleagues applied PRECIS-2 criteria to 5 pragmatic clinical trials (PCTs) being conducted through the NIH Collaboratory. Each trial was found to rate as “highly pragmatic” across the multiple PRECIS-2 domains, highlighting the tool’s potential usefulness in guiding decisions about study design, but also revealing a number of challenges in applying it and interpreting the results.
Study authors Johnson and Neta will be discussing their findings during the NIH Collaboratory’s Grand Rounds on Friday, January 22, 2016 (an archived version of the presentation will be available the following week).
Johnson KE, Neta G, Dember LM, Coronado GD, Suls J, Chambers DA, Rundell S, Smith DH, Liu B, Taplin S, Stoney CM, Farrell MM, Glasgow RE. Use of PRECIS ratings in the National Institutes of Health (NIH) Health Care Systems Research Collaboratory. Trials. 2016;17(1):32. doi: 10.1186/s13063-016-1158-y. PMID: 26772801. PMCID: PMC4715340.
You can read more about the NIH Collaboratory PCTs featured as part of this project at the following links:ABATE (Active Bathing to Eliminate Infection)
LIRE (A pragmatic trial of Lumbar Image Reporting with Epidemiology)
PPACT (Collaborative Care for Chronic Pain in Primary Care)
STOP-CRC (Strategies & Opportunities to Stop Colon Cancer in Priority Populations)
TIME (Time to Reduce Mortality in End-Stage Renal Disease)
Additional Resources
An introductory slide set on PCTs (by study author Karin Johnson) is available from the Living Textbook:
Introduction to Pragmatic Clinical Trials
The University of Colorado Denver - Anschutz Medical Campus publishes an electronic textbook on pragmatic trials:
Pragmatic Trials: A workshop Handbook
ABATE is a cluster-randomized trial that will evaluate different strategies for preventing hospital-acquired infections, including methicillin-resistant Staphylococcus aureus (MRSA) infections, a potentially serious complication and one that is particularly dangerous in intensive care units, although MRSA is known to create problems across a wide range of settings.
Dr. Huang was one 10 winners of CRF Research Achievement Awards, which are presented annually. A key report related to the ABATE project was published in the New England Journal of Medicine in June of 2013.
The Agency for Healthcare Research and Quality (AHRQ) published a new Toolkit for Decolonization of Non-ICU Patients With Devices to help clinical teams implement a protocol to reduce bloodstream infections by approximately 30% in patients with specific medical devices.
