Contemporary clinical trials最新文献

Background

Ovarian cancer (OC) survivors commonly experience chronic symptoms including anxiety, depression, sleep disturbances, fatigue, physical symptoms, poor health-related quality of life (HRQOL), and a generally poor prognosis. Additionally, factors such as social isolation, stress, and depression are associated with key biological processes promoting tumor progression and poorer survival. Accessible psychosocial interventions to improve HRQOL and clinical outcomes are needed. This need is particularly true in rural settings where survivors may have less access to clinic-based support systems.

Methods

The Living Well Study, a cluster-randomized Phase II multi-site clinical trial, is designed to evaluate the efficacy of a group-based, web-delivered psychosocial intervention (Mindful Living) verses a Health Promotion active control (Healthy Lifestyles) in increasing HRQOL and decreasing perceived stress (primary outcomes), depressive mood, anxiety, and fatigue (secondary outcomes) for 256 OC survivors who are <5 years post-primary therapy. Mindful Living targets key concerns of OC survivors and teaches stress reduction skills and coping strategies utilizing cognitive behavioral, mindfulness, and acceptance and commitment therapies. Healthy Lifestyles provides lifestyle information including exercise, nutrition, sleep, and other survivorship topics. Interventions consist of 11 consecutive weekly group sessions lasting 1.5–2 h led by trained facilitators and two booster sessions. Participants complete psychosocial questionnaires at baseline, post-intervention, at 6-months, and at 12-months. A subset completes bloodspots for analysis of inflammatory biology.

Conclusion

Easily accessible psychosocial interventions addressing key concerns of OC survivors are an unmet need. The Mindful Living intervention has the potential to substantially enhance HRQOL and decrease distress in OC survivors.

Trial registration clinicaltrials.gov Identifier: NCT04533763

Background

The three types of evidence-based treatment options for adults with overweight and obesity – behavioral weight management, anti-obesity medications (AOM), and bariatric surgery – are underutilized in the Veterans Health Administration (VHA) system. Our objective in this manuscript is to describe the study protocol for an adequately powered randomized controlled trial (RCT) of a behavioral intervention: TOTAL (Teaching Obesity Treatment Options to Adult Learners) to increase patient uptake of obesity treatment.

Methods

In this multi-site, parallel, RCT, eligible Veterans with a body mass index [BMI] ≥ 27 who had not received obesity treatment within the past 12 months were randomly assigned to TOTAL or usual care. TOTAL involves watching an 18-min video that highlights obesity health risks, pros/cons of all three evidence-based obesity treatments, and expected treatment outcomes. It also includes motivational sessions delivered via televideo at 2 weeks, 6 months, and 12 months after the video (target n = 494 participants). The primary outcome is initiation of behavioral weight management treatment within 18 months of randomization. Secondary outcomes include sustained behavioral weight management treatment, initiation of AOM, bariatric surgery referral, and weight change across 18 months.

Conclusion

TOTAL, which seeks to increase delivery of weight management treatment within the largest integrated health system in the U.S., combines patient education with motivational interviewing components. If efficacious in this trial, further evaluation of intervention effectiveness and implementation throughout the VHA and other healthcare systems would be warranted.

Despite a growing body of literature in the area of recruitment modeling for multicenter studies, in practice, statistical models to predict enrollments are rarely used and when they are, they often rely on unrealistic assumptions. The time-dependent Poisson-Gamma model (tPG) is a recently developed flexible methodology which allows analysts to predict recruitments in an ongoing multicenter trial, and its performance has been validated on data from a cohort study. In this article, we illustrate and further validate the tPG model on recruitment data from randomized controlled trials. Additionally, in the appendix, we provide a practical and easy to follow guide to its implementation via the tPG R package. To validate the model, we show the predictive performance of the proposed methodology in forecasting the recruitment process of two HIV vaccine trials conducted by the HIV Vaccine Trials Network in multiple Sub-Saharan countries.

High blood pressure (BP) is the leading preventable risk factor for death, but only one in three patients achieve target BP control. A key contributor to this problem is poor population awareness of high BP, as the majority of patients are asymptomatic. The Shop-To-Stop Hypertension study is a multicenter, cluster-randomized controlled trial to identify, refer and follow adults in need of hypertension care, whilst raising population-wide awareness. In participants with high BP measured by SiSU Health Stations located in major hardware chain stores across New South Wales, Australia, we will determine whether text message-based nudges will encourage repeat BP checks and visits to their doctor. Based on pilot data, we anticipate 65,340 participants will be screened over 12 months, of which 18% will have high BP. Thirty hardware stores will be randomized (1:1) to: (i) Intervention: participants detected with high BP (≥140/≥90 mmHg) will receive text message-based nudges to return for a repeat SiSU Health Station BP check and to visit their general practitioner (GP) to check and manage their BP; (ii) Control: participants with high BP will not receive text messages. The primary outcome is the difference in the proportion of participants with high BP having a repeat BP check at hardware Health Stations in the intervention vs. control group at 12 months. This novel setting for screening utilises a novel ‘citizen science’ approach inviting the general public to perform their own BP screening at health kiosks and foster behavioral change. This will allow screening in a low-stress environment.

Background

Persons receiving prescription buprenorphine for opioid use disorder experience high rates of comorbid conditions such as chronic pain and depression, which present barriers to buprenorphine care retention. This paper describes the protocol of the TOPPS (Treating Opioid Patients' Pain and Sadness) study, which compares a values-based, behavioral activation intervention with a health education contact-control condition, with the aim of decreasing chronic pain and depression, and increasing buprenorphine care retention for persons with opioid use disorder.

Methods

This randomized controlled trial (RCT) enrolls and randomizes up to 250 participants currently being treated with buprenorphine to receive three months of either TOPPS, a six-session phone-based behavioral intervention, or a health education (HE) control condition. We compare the TOPPS intervention to HE on the following outcomes: 1) pain interference and pain severity over the 3-month treatment phrase; 2) depressive symptoms over the 3-month treatment phase; and 3) sustained improvements in pain interference, depressive symptoms, and buprenorphine treatment retention over the 12-month study period. We also examine mechanisms by which the intervention may reduce pain interference.

Discussion

This RCT explores a novel intervention to address chronic pain and depression for individuals receiving buprenorphine in office-based settings. TOPPS may lead to improved pain, depression, and substance use outcomes, and can utilize providers available within buprenorphine programs, broadening the disseminability of this intervention and heightening its public health impact.

Clinical Trial

#NCT03698669

Background

Burnout in primary care undermines worker well-being and patient care. Many factors contribute to burnout, including high workloads, emotional stress, and unsupportive supervisors. Formative evidence suggests that burnout might be reduced if clinic leaders hold quarterly and brief (∼30 min) one-on-one check-ins with team members to acknowledge and address work-life stressors (e.g., schedules, workflow breakdowns, time off requests). This paper describes the intervention protocol for a randomized controlled trial (RCT) designed to evaluate the effectiveness and process of the check-ins in reducing burnout among primary care professionals.

Methods

Two-arm RCT conducted at 12 primary care clinics of a healthcare system in the Pacific Northwest. Six clinics received an adaptive design, semi-structured intervention, including predefined training modules with evidence-based tactics to reduce burnout through the check-ins, followed by clinic-specific feedback sessions prior to offering and conducting quarterly leader-employee check-ins. Six clinics were randomized as waitlist controls. Burnout was measured using the Maslach Burnout Inventory (MBI) at baseline and at the 12-month follow-up. Secondary outcomes include organizational constraints, psychological safety, and supervisor support. Multilevel modeling and qualitative methods were applied to evaluate the effects and process of the intervention.

Conclusion

By focusing on modifiable work-life factors such as stressors and supervisor support, the check-ins intervention aims to reduce burnout rates among primary care professionals. Findings from this trial will shed light on the conditions upon which check-ins might reduce burnout. Results will also inform policies and interventions aimed at improving mental health and well-being in primary care settings.

ClinicalTrials.gov: ID NCT05436548

Background

There have only been two efficacy trials reporting a head-to-head comparison of medications and psychotherapy for PTSD, and neither was conducted in primary care. Therefore, this protocol paper describes a pragmatic trial that compares outcomes of primary care patients randomized to initially receive a brief trauma-focused psychotherapy or a choice of three antidepressants. In addition, because there are few trials examining the effectiveness of subsequent treatments for patients not responding to the initial treatment, this pragmatic trial also compares the outcomes of those switching or augmenting treatments.

Method

Patients screening positive for PTSD (n = 700) were recruited from the primary care clinics of 7 Federally Qualified Health Centers (FQHC) and 8 Department of Veterans Affairs (VA) Medical Centers and randomized in the ratio 1:1:2 to one of three treatment sequences: 1) selective serotonin reuptake inhibitor (SSRI) followed by augmentation with Written Exposure Therapy (WET), 2) SSRI followed by a switch to serotonin-norepinephrine reuptake inhibitor (SNRI), or 3) WET followed by a switch to SSRI. Participants complete surveys at baseline, 4 months, and 8 months. The primary outcome is PTSD symptom severity as measured by the PTSD Checklist (PCL-5).

Results

Average PCL-5 scores (M = 52.8, SD = 11.1) indicated considerable severity. The most common bothersome traumatic event for VA enrollees was combat (47.8%), and for FQHC enrollees was other (28.2%), followed by sexual assault (23.4%), and child abuse (19.8%). Only 22.4% were taking an antidepressant at baseline.

Conclusion

Results will help healthcare systems and clinicians make decisions about which treatments to offer to patients.

Background

Minimizing the use of blood component can reduce known and unknown blood transfusion risks, preserve blood bank resources, and decrease healthcare costs. Red Blood Cell (RBC) transfusion is common after cardiac surgery and associated with adverse perioperative outcomes, including mortality. Acute normovolemic hemodilution (ANH) may reduce bleeding and the need for blood product transfusion after cardiac surgery. However, its blood-saving effect and impact on major outcomes remain uncertain.

Methods

This is a single-blinded, multinational, pragmatic, randomized controlled trial with a 1:1 allocation ratio conducted in Tertiary and University hospitals. The study is designed to enroll patients scheduled for elective cardiac surgery with planned cardiopulmonary bypass (CPB). Patients are randomized to receive ANH before CPB or the best available treatment without ANH. We identified an ANH volume of at least 650 ml as the critical threshold for clinically relevant benefits. Larger ANH volumes, however, are allowed and tailored to the patient's characteristics and clinical conditions.

Results

The primary outcome is the percentage of patients receiving RBCs transfusion from randomization until hospital discharge, which we hypothesize will be reduced from 35% to 28% with ANH. Secondary outcomes are all-cause 30-day mortality, acute kidney injury, bleeding complications, and ischemic complications.

Conclusion

The trial is designed to determine whether ANH can safely reduce RBC transfusion after elective cardiac surgery with CPB.

Study registration

This trial was registered on ClinicalTrials.gov in April 2019 with the trial identification number NCT03913481.

Background

Missing outcome data is common in trials, and robust methods to address this are needed. Most trial reports currently use methods applicable under a missing completely at random assumption (MCAR), although this strong assumption can often be inappropriate.

Objective

To identify and summarise current literature on the analytical methods for handling missing outcome data in randomised controlled trials (RCTs), emphasising methods appropriate for data missing at random (MAR) or missing not at random (MNAR).

Study design and setting

We conducted a methodological scoping review and identified papers through searching four databases (MEDLINE, Embase, CENTRAL, and CINAHL) from January 2015 to March 2023. We also performed forward and backward citation searching. Eligible papers discussed methods or frameworks for handling missing outcome data in RCTs or simulation studies with an RCT design.

Results

From 1878 records screened, our search identified 101 eligible papers. 90 (89%) papers described specific methods for addressing missing outcome data and 11 (11%) described frameworks for overall methodological approach. Of the 90 methods papers, 30 (33%) described methods under the MAR assumption, 48 (53%) explored methods under the MNAR assumption and 11 (12%) discussed methods under a hybrid of MAR and MNAR assumptions. Control-based methods under the MNAR assumption were the most common method explored, followed by multiple imputation under the MAR assumption.

Conclusion

This review provides guidance on available analytic approaches for handling missing outcome data, particularly under the MNAR assumption. These findings may support trialists in using appropriate methods to address missing outcome data.