Browsing by Subject "Randomized controlled trials"

Now showing 1 - 7 of 7
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    Biomarker disclosure protocols in prodromal Alzheimer’s disease clinical trials
    (Wiley, 2023) Rahman-Filipiak, Annalise; Bolton, Corey; Grill, Joshua D.; Rostamzadeh, Ayda; Chin, Nathaniel; Heidebrink, Judith; Getz, Sarah; Fowler, Nicole R.; Rosen, Allyson; Lingler, Jennifer; Wijsman, Ellen; Clark, Lindsay; Advisory Group on Risk Evidence Education in Dementia (AGREED); Medicine, School of Medicine
    Introduction: The development of biomarkers for Alzheimer's disease (AD) has allowed researchers to increase sample homogeneity and test candidate treatments earlier in the disease. The integration of biomarker "screening" criteria should be met with a parallel implementation of standardized methods to disclose biomarker testing results to research participants; however, the extent to which protocolized disclosure occurs in trials is unknown. Methods: We reviewed the literature to identify prodromal AD trials published in the past 10 years. From these, we quantified the frequency of biomarker disclosure reporting and the depth of descriptions provided. Results: Of 30 published trials using positron emission tomography or cerebrospinal fluid-based amyloid positivity as an eligibility criterion, only one mentioned disclosure, with no details on methods. Discussion: Possible reasons for and implications of this information gap are discussed. Recommendations are provided for trialists considering biomarker screening as part of intervention trials focused on prodromal AD. Highlights: Few prodromal Alzheimer's disease (AD) trial papers discuss biomarker disclosure. Disclosure has implications for participants, family members, and trial success. Disclosure must be consistently integrated and reported in prodromal AD trials. Best practice guidelines and training resources for disclosure are needed.
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    Disease-modifying therapies and features linked to treatment response in type 1 diabetes prevention: a systematic review
    (Springer Nature, 2023-10-05) Felton, Jamie L.; Griffin, Kurt J.; Oram, Richard A.; Speake, Cate; Long, S. Alice; Onengut-Gumuscu, Suna; Rich, Stephen S.; Monaco, Gabriela S. F.; Evans-Molina, Carmella; DiMeglio, Linda A.; Ismail, Heba M.; Steck, Andrea K.; Dabelea, Dana; Johnson, Randi K.; Urazbayeva, Marzhan; Gitelman, Stephen; Wentworth, John M.; Redondo, Maria J.; Sims, Emily K.; Pediatrics, School of Medicine
    Background: Type 1 diabetes (T1D) results from immune-mediated destruction of insulin-producing beta cells. Prevention efforts have focused on immune modulation and supporting beta cell health before or around diagnosis; however, heterogeneity in disease progression and therapy response has limited translation to clinical practice, highlighting the need for precision medicine approaches to T1D disease modification. Methods: To understand the state of knowledge in this area, we performed a systematic review of randomized-controlled trials with ≥50 participants cataloged in PubMed or Embase from the past 25 years testing T1D disease-modifying therapies and/or identifying features linked to treatment response, analyzing bias using a Cochrane-risk-of-bias instrument. Results: We identify and summarize 75 manuscripts, 15 describing 11 prevention trials for individuals with increased risk for T1D, and 60 describing treatments aimed at preventing beta cell loss at disease onset. Seventeen interventions, mostly immunotherapies, show benefit compared to placebo (only two prior to T1D onset). Fifty-seven studies employ precision analyses to assess features linked to treatment response. Age, beta cell function measures, and immune phenotypes are most frequently tested. However, analyses are typically not prespecified, with inconsistent methods of reporting, and tend to report positive findings. Conclusions: While the quality of prevention and intervention trials is overall high, the low quality of precision analyses makes it difficult to draw meaningful conclusions that inform clinical practice. To facilitate precision medicine approaches to T1D prevention, considerations for future precision studies include the incorporation of uniform outcome measures, reproducible biomarkers, and prespecified, fully powered precision analyses into future trial design.
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    Engaging Clinical Nurses in Research: Nurses’ Experiences Delivering a Communication Intervention in a Behavioral Oncology Clinical Trial
    (Lippincott, Williams & Wilkins, 2020-04-01) Landon, Leslie; Crane, Stacey; Nance, Stacy; Stegenga, Kristin; Cherven, Brooke; Perez Prado, Luz N.; Butrum, Karen Dawn; Beacham, Barbara; Haase, Joan E.; School of Nursing
    Despite the recognized need for clinical nurses to engage in the conduct of research, little is known about their research experiences. This article describes the experiences of nurses who delivered the communication intervention in a behavioral oncology clinical trial for parents of adolescents and young adults (AYAs) with cancer. A qualitative thematic analysis was conducted of nurse interveners’ (NIs’) reflections on their experiences delivering the communication intervention. Ten data-generating questions were developed to guide NIs’ reflections. Twelve NIs responded via verbal discussions. Six of these also provided written responses. Overall, nurses’ experiences as interveners were powerful and positive, and included time and space to be fully present with patients and families. NIs identified barriers to their involvement in research related to time constraints, administrative support, physical space to privately conduct the intervention, and difficulties maintaining expertise with the intervention. The importance of ongoing collaboration between nurses, unit staff, leaders, and study teams was corroborated. An unexpected finding was the importance of Reflective Clinical Research.
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    Findings and Future Directions from a Smoking Cessation Trial Utilizing a Clinical Decision Support Tool
    (Elsevier, 2022-09) Rindal, Donald Brad; Kottke, Thomas E.; Jurkovich, Mark W.; Asche, Stephen E.; Enstad , Chris J.; Truitt, Anjali R.; Ziegenfuss, Jeanette Y.; Romito, Laura M.; Thyvalikakath, Thankam P.; O'Donnell, Jean; Spallek, Heiko; Dental Public Health and Dental Informatics, School of Dentistry
    Background Tobacco smoking is the leading cause of disease, death, and disability in the United States. Dental practitioners are advised to provide evidence-based smoking cessation interventions to their patients, yet dental practitioners frequently fail to deliver brief smoking cessation advice. Objectives To test whether giving dental practitioners a clinical decisions support (CDS) system embedded in their electronic dental record would increase the rate at which patients who smoke (1) report receiving a brief intervention or referral to treatment during a recent dental visit, (2) taking action related to smoking cessation within 7 days of visit, and (3) stop smoking for 1 day or more or reduce the amount smoked by 50% within 6 months. Methods Two-group, parallel arm, cluster-randomized trial. From March through December 2019, 15 nonacademic primary care dental clinics were randomized via covariate adaptive randomization to either a usual care arm or the CDS arm. Adult smokers completed an initial telephone survey within 7 days of their visit and another survey after 6 months. Results Forty-three patients from 5 CDS and 13 patients from 2 usual care clinics completed the 7-day survey. While the proportion of patients who reported receipt of a brief intervention or referral to treatment was significantly greater in the CDS arm than the usual care arm (84.3% vs 58.6%; P = .005), the differences in percentage of patients who took any action related to smoking cessation within 7 days (44.4% vs 22.3%; P = .077), or stopped smoking for one day or more and/or reduced amount smoked by 50% within 6 months (63.1% vs 46.2%; P = .405) were large but not statistically significant. Conclusions Despite interruption by COVID-19, these results demonstrate a promising approach to assist dental practitioners in providing their patients with smoking cessation screening, brief intervention and referral to treatment.
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    Hyperkalemia Risk with Finerenone: Results from the FIDELIO-DKD Trial
    (Wolters Kluwer, 2022) Agarwal, Rajiv; Joseph, Amer; Anker, Stefan D.; Filippatos, Gerasimos; Rossing, Peter; Ruilope, Luis M.; Pitt, Bertram; Kolkhof, Peter; Scott, Charlie; Lawatscheck, Robert; Wilson, Daniel J.; Bakris, George L.; FIDELIO-DKD Investigators; Medicine, School of Medicine
    Background: Finerenone reduced risk of cardiorenal outcomes in patients with CKD and type 2 diabetes in the FIDELIO-DKD trial. We report incidences and risk factors for hyperkalemia with finerenone and placebo in FIDELIO-DKD. Methods: This post hoc safety analysis defined hyperkalemia as ≥mild or ≥moderate based on serum potassium concentrations of >5.5 or >6.0 mmol/L, respectively, assessed at all regular visits. Cumulative incidences of hyperkalemia were based on the Aalen-Johansen estimator using death as competing risk. A multivariate Cox proportional hazards model identified significant independent predictors of hyperkalemia. Restricted cubic splines assessed relationships between short-term post-baseline changes in serum potassium or eGFR and subsequent hyperkalemia risk. During the study, serum potassium levels guided drug dosing. Patients in either group who experienced ≥mild hyperkalemia had the study drug withheld until serum potassium was ≤5.0 mmol/L; then the drug was restarted at the 10 mg daily dose. Placebo-treated patients underwent sham treatment interruption and downtitration. Results: Over 2.6 years' median follow-up, 597 of 2785 (21.4%) and 256 of 2775 (9.2%) patients treated with finerenone and placebo, respectively, experienced treatment-emergent ≥mild hyperkalemia; 126 of 2802 (4.5%) and 38 of 2796 (1.4%) patients, respectively, experienced moderate hyperkalemia. Independent risk factors for ≥mild hyperkalemia were higher serum potassium, lower eGFR, increased urine albumin-creatinine ratio, younger age, female sex, β-blocker use, and finerenone assignment. Diuretic or sodium-glucose cotransporter-2 inhibitor use reduced risk. In both groups, short-term increases in serum potassium and decreases in eGFR were associated with subsequent hyperkalemia. At month 4, the magnitude of increased hyperkalemia risk for any change from baseline was smaller with finerenone than with placebo. Conclusions: Finerenone was independently associated with hyperkalemia. However, routine potassium monitoring and hyperkalemia management strategies employed in FIDELIO-DKD minimized the impact of hyperkalemia, providing a basis for clinical use of finerenone.
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    Kidney, Cardiovascular, and Safety Outcomes of Canagliflozin according to Baseline Albuminuria: A CREDENCE Secondary Analysis
    (Wolters Kluwer, 2021) Jardine, Meg; Zhou, Zien; Lambers Heerspink, Hiddo J.; Hockham, Carinna; Li, Qiang; Agarwal, Rajiv; Bakris, George L.; Cannon, Christopher P.; Charytan, David M.; Greene, Tom; Levin, Adeera; Li, Jing-Wei; Neuen, Brendon L.; Neal, Bruce; Oh, Richard; Oshima, Megumi; Pollock, Carol; Wheeler, David C.; de Zeeuw, Dick; Zhang, Hong; Zinman, Bernard; Mahaffey, Kenneth W.; Perkovic, Vlado; Medicine, School of Medicine
    Background and objectives: The kidney protective effects of renin-angiotensin system inhibitors are greater in people with higher levels of albuminuria at treatment initiation. Whether this applies to sodium-glucose cotransporter 2 (SGLT2) inhibitors is uncertain, particularly in patients with a very high urine albumin-to-creatinine ratio (UACR; ≥3000 mg/g). We examined the association between baseline UACR and the effects of the SGLT2 inhibitor, canagliflozin, on efficacy and safety outcomes in the Canagliflozin and Renal Endpoints in Diabetes with Established Nephropathy Clinical Evaluation (CREDENCE) randomized controlled trial. Design, setting, participants, & measurements: The study enrolled 4401 participants with type 2 diabetes, an eGFR of 30 to <90 ml/min per 1.73 m2, and UACR of >300 to 5000 mg/g. Using Cox proportional hazards regression, we examined the relative and absolute effects of canagliflozin on kidney, cardiovascular, and safety outcomes according to a baseline UACR of ≤1000 mg/g (n=2348), >1000 to <3000 mg/g (n=1547), and ≥3000 mg/g (n=506). In addition, we examined the effects of canagliflozin on UACR itself, eGFR slope, and the intermediate outcomes of glycated hemoglobin, body weight, and systolic BP. Results: Overall, higher UACR was associated with higher rates of kidney and cardiovascular events. Canagliflozin reduced efficacy outcomes for all UACR levels, with no evidence that relative benefits varied between levels. For example, canagliflozin reduced the primary composite outcome by 24% (hazard ratio [HR], 0.76; 95% confidence interval [95% CI], 0.56 to 1.04) in the lowest UACR subgroup, 28% (HR, 0.72; 95% CI, 0.56 to 0.93) in the UACR subgroup >1000 to <3000 mg/g, and 37% (HR, 0.63; 95% CI, 0.47 to 0.84) in the highest subgroup (Pheterogeneity=0.55). Absolute risk reductions for kidney outcomes were greater in participants with higher baseline albuminuria; the number of primary composite events prevented across ascending UACR categories were 17 (95% CI, 3 to 38), 45 (95% CI, 9 to 81), and 119 (95% CI, 35 to 202) per 1000 treated participants over 2.6 years (Pheterogeneity=0.02). Rates of kidney-related adverse events were lower with canagliflozin, with a greater relative reduction in higher UACR categories. Conclusions: Canagliflozin safely reduces kidney and cardiovascular events in people with type 2 diabetes and severely increased albuminuria. In this population, the relative kidney benefits were consistent over a range of albuminuria levels, with greatest absolute kidney benefit in those with an UACR ≥3000 mg/g.
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    Setting the dry weight and its cardiovascular implications
    (Wiley, 2017-11) Sinha, Arjun D.; Agarwal, Rajiv; Medicine, School of Medicine
    Volume overload is common and associated with adverse outcomes in the hemodialysis population including systemic hypertension, pulmonary hypertension, left ventricular hypertrophy, and mortality. Since the beginning of the era of maintenance dialysis, prescribing and maintaining a dry weight remains the standard of care for managing volume overload on hemodialysis. Reducing dry weight even by relatively small amounts has been shown to improve blood pressure and has been associated with reductions in left ventricular hypertrophy. Maintaining an adequately low dry weight requires attention to sodium intake and adequate time on dialysis, as well as a high index of suspicion for volume overload. Reducing dry weight can provoke decreased cardiac chamber filling and is associated with risks including intradialytic hypotension. The ideal method to minimize intradialytic morbidity is unknown, but more frequent dialysis should be considered. Experimental methods of assessing volume status may allow identification of patients most likely both to tolerate and to benefit from dry weight reduction, but further study is needed.