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Trials Jun 2024Most patients starting chronic in-center hemodialysis (HD) receive conventional hemodialysis (CHD) with three sessions per week targeting specific biochemical clearance....
Comparative effectiveness of an individualized model of hemodialysis vs conventional hemodialysis: a study protocol for a multicenter randomized controlled trial (the TwoPlus trial).
BACKGROUND
Most patients starting chronic in-center hemodialysis (HD) receive conventional hemodialysis (CHD) with three sessions per week targeting specific biochemical clearance. Observational studies suggest that patients with residual kidney function can safely be treated with incremental prescriptions of HD, starting with less frequent sessions and later adjusting to thrice-weekly HD. This trial aims to show objectively that clinically matched incremental HD (CMIHD) is non-inferior to CHD in eligible patients.
METHODS
An unblinded, parallel-group, randomized controlled trial will be conducted across diverse healthcare systems and dialysis organizations in the USA. Adult patients initiating chronic hemodialysis (HD) at participating centers will be screened. Eligibility criteria include receipt of fewer than 18 treatments of HD and residual kidney function defined as kidney urea clearance ≥3.5 mL/min/1.73 m and urine output ≥500 mL/24 h. The 1:1 randomization, stratified by site and dialysis vascular access type, assigns patients to either CMIHD (intervention group) or CHD (control group). The CMIHD group will be treated with twice-weekly HD and adjuvant pharmacologic therapy (i.e., oral loop diuretics, sodium bicarbonate, and potassium binders). The CHD group will receive thrice-weekly HD according to usual care. Throughout the study, patients undergo timed urine collection and fill out questionnaires. CMIHD will progress to thrice-weekly HD based on clinical manifestations or changes in residual kidney function. Caregivers of enrolled patients are invited to complete semi-annual questionnaires. The primary outcome is a composite of patients' all-cause death, hospitalizations, or emergency department visits at 2 years. Secondary outcomes include patient- and caregiver-reported outcomes. We aim to enroll 350 patients, which provides ≥85% power to detect an incidence rate ratio (IRR) of 0.9 between CMIHD and CHD with an IRR non-inferiority of 1.20 (α = 0.025, one-tailed test, 20% dropout rate, average of 2.06 years of HD per patient participant), and 150 caregiver participants (of enrolled patients).
DISCUSSION
Our proposal challenges the status quo of HD care delivery. Our overarching hypothesis posits that CMIHD is non-inferior to CHD. If successful, the results will positively impact one of the highest-burdened patient populations and their caregivers.
TRIAL REGISTRATION
Clinicaltrials.gov NCT05828823. Registered on 25 April 2023.
Topics: Humans; Renal Dialysis; Multicenter Studies as Topic; Treatment Outcome; Time Factors; Comparative Effectiveness Research; Randomized Controlled Trials as Topic; Equivalence Trials as Topic; United States; Kidney Failure, Chronic
PubMed: 38943204
DOI: 10.1186/s13063-024-08281-9 -
Malaria Journal Jun 2024Microscopic detection of malaria parasites is labour-intensive, time-consuming, and expertise-demanding. Moreover, the slide interpretation is highly dependent on the...
BACKGROUND
Microscopic detection of malaria parasites is labour-intensive, time-consuming, and expertise-demanding. Moreover, the slide interpretation is highly dependent on the staining technique and the technician's expertise. Therefore, there is a growing interest in next-generation, fully- or semi-integrated microscopes that can improve slide preparation and examination. This study aimed to evaluate the clinical performance of miLab™ (Noul Inc., Republic of Korea), a fully-integrated automated microscopy device for the detection of malaria parasites in symptomatic patients at point-of-care in Sudan.
METHODS
This was a prospective, case-control diagnostic accuracy study conducted in primary health care facilities in rural Khartoum, Sudan in 2020. According to the outcomes of routine on-site microscopy testing, 100 malaria-positive and 90 malaria-negative patients who presented at the health facility and were 5 years of age or older were enrolled consecutively. All consenting patients underwent miLab™ testing and received a negative or suspected result. For the primary analysis, the suspected results were regarded as positive (automated mode). For the secondary analysis, the operator reviewed the suspected results and categorized them as either negative or positive (corrected mode). Nested polymerase chain reaction (PCR) was used as the reference standard, and expert light microscopy as the comparator.
RESULTS
Out of the 190 patients, malaria diagnosis was confirmed by PCR in 112 and excluded in 78. The sensitivity of miLab™ was 91.1% (95% confidence interval [CI] 84.2-95.6%) and the specificity was 66.7% (95% Cl 55.1-67.7%) in the automated mode. The specificity increased to 96.2% (95% Cl 89.6-99.2%), with operator intervention in the corrected mode. Concordance of miLab with expert microscopy was substantial (kappa 0.65 [95% CI 0.54-0.76]) in the automated mode, but almost perfect (kappa 0.97 [95% CI 0.95-0.99]) in the corrected mode. A mean difference of 0.359 was found in the Bland-Altman analysis of the agreement between expert microscopy and miLab™ for quantifying parasite counts.
CONCLUSION
When used in a clinical context, miLab™ demonstrated high sensitivity but low specificity. Expert intervention was shown to be required to improve the device's specificity in its current version. miLab™ in the corrected mode performed similar to expert microscopy. Before clinical application, more refinement is needed to ensure full workflow automation and eliminate human intervention. Trial registration ClinicalTrials.gov: NCT04558515.
Topics: Sudan; Microscopy; Humans; Case-Control Studies; Prospective Studies; Point-of-Care Systems; Female; Male; Sensitivity and Specificity; Child; Child, Preschool; Adult; Adolescent; Malaria; Young Adult; Middle Aged
PubMed: 38943203
DOI: 10.1186/s12936-024-05029-3 -
Trials Jun 2024Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy...
Biomarker Driven Antifungal Stewardship (BioDriveAFS) in acute leukaemia-a multi-centre randomised controlled trial to assess clinical and cost effectiveness: a study protocol for a randomised controlled trial.
BACKGROUND
Acute leukaemias (AL) are life-threatening blood cancers that can be potentially cured with treatment involving myelosuppressive, multiagent, intensive chemotherapy (IC). However, such treatment is associated with a risk of serious infection, in particular invasive fungal infection (IFI) associated with prolonged neutropenia. Current practice guidelines recommend primary antifungal (AF) prophylaxis to be administered to high-risk patients to reduce IFI incidence. AFs are also used empirically to manage prolonged neutropenic fever. Current strategies lead to substantial overuse of AFs. Galactomannan (GM) and β-D-glucan (BG) biomarkers are also used to diagnose IFI. Combining both biomarkers may enhance the predictability of IFI compared to administering each test alone. Currently, no large-scale randomised controlled trial (RCT) has directly compared a biomarker-based diagnostic screening strategy without AF prophylaxis to AF prophylaxis (without systematic biomarker testing).
METHODS
BioDriveAFS is a multicentre, parallel, two-arm RCT of 404 participants from UK NHS Haematology departments. Participants will be allocated on a 1:1 basis to receive either a biomarker-based antifungal stewardship (AFS) strategy, or a prophylactic AF strategy, which includes existing standard of care (SoC). The co-primary outcomes will be AF exposure in the 12-month post randomisation and the patient-reported EQ-5D-5L measured at 12-month post randomisation. Secondary outcomes will include total AF exposure, probable/proven IFI, survival (all-cause mortality and IFI mortality), IFI treatment outcome, AF-associated adverse effects/events/complications, resource use, episodes of neutropenic fever requiring hospital admission or outpatient management, AF resistance in fungi (non-invasive and invasive) and a Desirability of Outcome Ranking. The trial will have an internal pilot phase during the first 9 months. A mixed methods process evaluation will be integrated in parallel to the internal pilot phase and full trial, aiming to robustly assess how the intervention is delivered. Cost-effectiveness analysis will also be performed.
DISCUSSION
The BioDriveAFS trial aims to further the knowledge of strategies that will safely optimise AF use through comparison of the clinical and cost-effectiveness of a biomarker-led diagnostic strategy versus prophylactic AF to prevent and manage IFI within acute leukaemia. The evidence generated from the study will help inform global clinical practice and approaches within antifungal stewardship.
TRIAL REGISTRATION
ISRCTN11633399. Registered 24/06/2022.
Topics: Humans; Antifungal Agents; Cost-Benefit Analysis; Randomized Controlled Trials as Topic; Invasive Fungal Infections; Multicenter Studies as Topic; Biomarkers; Galactose; Mannans; Treatment Outcome; beta-Glucans; Antimicrobial Stewardship; Leukemia; Time Factors; Cost-Effectiveness Analysis
PubMed: 38943201
DOI: 10.1186/s13063-024-08272-w -
Critical Care (London, England) Jun 2024In a phase 3 trial (PANAMO, NCT04333420), vilobelimab, a complement 5a (C5a) inhibitor, reduced 28-day mortality in mechanically ventilated COVID-19 patients. This post... (Randomized Controlled Trial)
Randomized Controlled Trial
In a phase 3 trial (PANAMO, NCT04333420), vilobelimab, a complement 5a (C5a) inhibitor, reduced 28-day mortality in mechanically ventilated COVID-19 patients. This post hoc analysis of 368 patients aimed to explore treatment heterogeneity through unsupervised learning. All available clinical variables at baseline were used as input. Treatment heterogeneity was assessed using latent class analysis (LCA), Ward's hierarchical clustering (HC) and the adjudication to previously described clinical sepsis phenotypes. The primary outcome was 28-day mortality. For LCA, a 2-class latent model was deemed most suitable. In the LCA model, 82 (22%) patients were assigned to class 1 and 286 (78%) to class 2. Class 1 was defined by more severely ill patients with significantly higher mortality. In an adjusted logistic regression, no heterogeneity of treatment effect (HTE) between classes was observed (p = 0.998). For HC, no significant classes were found (p = 0.669). Using the previously described clinical sepsis subtypes, 41 patients (11%) were adjudicated subtype alpha (α), 17 (5%) beta (β), 112 (30%) delta (δ) and 198 (54%) gamma (γ). HTE was observed between clinical subtypes (p = 0.001) with improved 28-day mortality after treatment with vilobelimab for the δ subtype (OR = 0.17, 95% CI 0.07-0.40, p < 0.001). No signal for harm of treatment with vilobelimab was observed in any class or clinical subtype. Overall, treatment effect with vilobelimab was consistent across different classes and subtypes, except for the δ subtype, suggesting potential additional benefit for the most severely ill patients.
Topics: Humans; Female; Male; Middle Aged; Aged; COVID-19 Drug Treatment; Antibodies, Monoclonal, Humanized; Treatment Outcome; COVID-19
PubMed: 38943192
DOI: 10.1186/s13054-024-05004-z -
Trials Jun 2024Isolated REM sleep behavior disorder (iRBD) is an early α-synucleinopathy often accompanied by incipient cognitive impairment. As executive dysfunctions predict earlier...
Cognitive training and promoting a healthy lifestyle for individuals with isolated REM sleep behavior disorder: study protocol of the delayed-start randomized controlled trial CogTrAiL-RBD.
BACKGROUND
Isolated REM sleep behavior disorder (iRBD) is an early α-synucleinopathy often accompanied by incipient cognitive impairment. As executive dysfunctions predict earlier phenotypic conversion from iRBD to Parkinson's disease and Lewy body dementia, cognitive training focusing on executive functions could have disease-modifying effects for individuals with iRBD.
METHODS
The study CogTrAiL-RBD investigates the short- and long-term effectiveness and the feasibility and underlying neural mechanisms of a cognitive training intervention for individuals with iRBD. The intervention consists of a 5-week digital cognitive training accompanied by a module promoting a healthy, active lifestyle. In this monocentric, single-blinded, delayed-start randomized controlled trial, the intervention's effectiveness will be evaluated compared to an initially passive control group that receives the intervention in the second, open-label phase of the study. Eighty individuals with iRBD confirmed by polysomnography will be consecutively recruited from the continuously expanding iRBD cohort at the University Hospital Cologne. The evaluation will focus on cognition and additional neuropsychological and motor variables. Furthermore, the study will examine the feasibility of the intervention, effects on physical activity assessed by accelerometry, and interrogate the intervention's neural effects using magnetic resonance imaging and polysomnography. Besides, a healthy, age-matched control group (HC) will be examined at the first assessment time point, enabling a cross-sectional comparison between individuals with iRBD and HC.
DISCUSSION
This study will provide insights into whether cognitive training and psychoeducation on a healthy, active lifestyle have short- and long-term (neuro-)protective effects for individuals with iRBD.
TRIAL REGISTRATION
The study was prospectively registered in the German Clinical Trial Register (DRKS00024898) on 2022-03-11, https://drks.de/search/de/trial/DRKS00024898 .
PROTOCOL VERSION
V5 2023-04-24.
Topics: Humans; Single-Blind Method; REM Sleep Behavior Disorder; Healthy Lifestyle; Randomized Controlled Trials as Topic; Executive Function; Cognition; Time Factors; Polysomnography; Treatment Outcome; Cognitive Behavioral Therapy; Male; Germany; Middle Aged; Exercise; Female; Aged; Feasibility Studies; Cognitive Training
PubMed: 38943191
DOI: 10.1186/s13063-024-08265-9 -
Trials Jun 2024Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks' gestation have low vitamin D levels at birth and a...
BACKGROUND
Vitamin D is necessary to develop healthy lungs and other organs early in life. Most infants born before 28 weeks' gestation have low vitamin D levels at birth and a limited intake during the first month. Enteral vitamin D supplementation is inexpensive and widely used. The appropriate supplementation regimen for extremely preterm infants is controversial, and the effect of different regimens on their blood levels and outcomes is unclear.
METHODS
Randomized, blinded comparative effectiveness trial to compare two vitamin D supplementation regimens for inborn infants <28 weeks gestation or <1000 g birth weight at a large academic center in the United States. Infants are stratified by birth weight and randomized within 96 h after birth to either routine supplementation (400 IU/day with established feedings) or increased supplementation (800 IU/day with any feedings) during the first 28 days after birth. We hypothesize that the higher and early vitamin D dose (800 IU/day with early feeding) compared to placebo plus routine dose (400 IU/day with established feeding) will substantially increase total 25-hydroxyvitamin D3 levels measured as state-of-art at 1 month, reduce respiratory support at 36 weeks' postmenstrual age (on an ordinal scale predictive of later adverse outcomes), and improve or at least not worsen other important secondary outcomes. The infants in the study will follow up at 22-26 months' corrected age (~2 years) with blinded certified examiners to evaluate neurodevelopmental outcomes. The sample size of a minimum of 180 infants provides >90% power to detect a >95% posterior probability of a 33% increase in serum 25-hydroxy vitamin D3 and >80% power to detect a >80% posterior probability of a relative risk decrease of 20% of reducing respiratory support by intention-to-treat Bayesian analyses using a neutral prior probability.
DISCUSSION
Our study will help clarify the uncertain relationship of vitamin D supplementation and its associated serum metabolites to clinical outcomes of extremely preterm infants. Confirmation of our hypotheses would prompt reconsideration of the supplementation regimens used in extremely preterm infants and justify a large multicenter study to verify the generalizability of the results.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05459298. Registered on July 14, 2022.
Topics: Humans; Infant, Newborn; Gestational Age; Dietary Supplements; Randomized Controlled Trials as Topic; Vitamin D; Birth Weight; Enteral Nutrition; Vitamin D Deficiency; Treatment Outcome; Infant, Extremely Premature; Time Factors; Female; Vitamins; Calcifediol; Male
PubMed: 38943179
DOI: 10.1186/s13063-024-08274-8 -
Journal of Orthopaedic Surgery and... Jun 2024Our study aims to assess the effectiveness of multicomponent supervised tele-rehabilitation compared to home-based self-rehabilitation management in patients following... (Comparative Study)
Comparative Study Randomized Controlled Trial
Multicomponent supervised tele-rehabilitation versus home-based self-rehabilitation management after anterior cruciate ligament reconstruction: a study protocol for a randomized controlled trial.
INTRODUCTION
Our study aims to assess the effectiveness of multicomponent supervised tele-rehabilitation compared to home-based self-rehabilitation management in patients following anterior cruciate ligament reconstruction (ACLR).
METHODS
The current study is designed as a single-center, single-blinded, randomized controlled, two-arm trial. Participants will be randomized and allocated at a 1:1 ratio into either a multicomponent supervised tele-rehabilitation group or a home-based self-rehabilitation group. All participants receive uniform preoperative education through the HJT software. Participants in the intervention group undergo multicomponent supervised tele-rehabilitation, while those in the control group follow a home-based self-rehabilitation program. All the participants were assessed and measured for the included outcomes at the outpatient clinic before the procedure, and in 2, 4, 8, 12, and 24 weeks after ACLR by two assessors. The primary outcome was the percentage of patients who achieve a satisfactory active ROM at the 12 weeks following the ACLR. The satisfactory active ROM was also collected at 2, 4, 8, and 24 weeks after ACLR. The secondary outcomes were active and passive range of motion (ROM), pain, muscle strength, and function results.
REGISTRATION DETAILS
Ethical approval has been obtained from the West China Hospital Ethics Committee (approval number 2023-1929, December 2023). The trial has been registered on ClinicalTrials.gov (registration number NCT06232824, January 2024).
Topics: Humans; Anterior Cruciate Ligament Reconstruction; Telerehabilitation; Single-Blind Method; Range of Motion, Articular; Treatment Outcome; Adult; Male; Female; Young Adult; Home Care Services; Randomized Controlled Trials as Topic; Anterior Cruciate Ligament Injuries; Muscle Strength; Adolescent
PubMed: 38943178
DOI: 10.1186/s13018-024-04871-0 -
Trials Jun 2024Bladder dysfunction, notably urinary retention, emerges as a significant complication for cervical cancer patients following radical hysterectomy, predominantly due to...
Evaluating the effectiveness of early urethral catheter removal combined with intermittent catheterization for promoting early recovery of bladder function after laparoscopic radical hysterectomy: a study protocol for a randomized controlled trial.
BACKGROUND
Bladder dysfunction, notably urinary retention, emerges as a significant complication for cervical cancer patients following radical hysterectomy, predominantly due to nerve damage, severely impacting their postoperative quality of life. The challenges to recovery include insufficient pelvic floor muscle training and the negative effects of prolonged postoperative indwelling urinary catheters. Intermittent catheterization represents the gold standard for neurogenic bladder management, facilitating bladder training, which is an important behavioral therapy aiming to enhance bladder function through the training of the external urethral sphincter and promoting the recovery of the micturition reflex. Nevertheless, gaps remain in current research regarding optimal timing for intermittent catheterization and the evaluation of subjective symptoms of bladder dysfunction.
METHODS
Cervical cancer patients undergoing laparoscopic radical hysterectomy will be recruited to this randomized controlled trial. Participants will be randomly assigned to either early postoperative catheter removal combined with intermittent catheterization group or a control group receiving standard care with indwelling urinary catheters. All these patients will be followed for 3 months after surgery. The study's primary endpoint is the comparison of bladder function recovery rates (defined as achieving a Bladder Function Recovery Grade of II or higher) 2 weeks post-surgery. Secondary endpoints include the incidence of urinary tract infections, and changes in urodynamic parameters, and Mesure Du Handicap Urinaire scores within 1 month postoperatively. All analysis will adhere to the intention-to-treat principle.
DISCUSSION
The findings from this trial are expected to refine clinical management strategies for enhancing postoperative recovery among cervical cancer patients undergoing radical hysterectomy. By providing robust evidence, this study aims to support patients and their families in informed decision-making regarding postoperative bladder management, potentially reducing the incidence of urinary complications and improving overall quality of life post-surgery.
TRIAL REGISTRATION
ChiCTR2200064041, registered on 24th September, 2022.
Topics: Humans; Hysterectomy; Female; Urinary Bladder; Laparoscopy; Recovery of Function; Uterine Cervical Neoplasms; Randomized Controlled Trials as Topic; Urinary Catheters; Intermittent Urethral Catheterization; Time Factors; Device Removal; Treatment Outcome; Quality of Life; Urodynamics; Middle Aged; Urinary Retention; Adult; Urinary Catheterization; Catheters, Indwelling
PubMed: 38943177
DOI: 10.1186/s13063-024-08266-8 -
Trials Jun 2024Social isolation and loneliness (SIL) worsens mortality and other outcomes among older adults as much as smoking. We previously tested the impact of the HOW R U?...
Impact of an intergenerational program to improve loneliness and social isolation in older adults initiated at the time of emergency department discharge: study protocol for a three-arm randomized clinical trial.
BACKGROUND
Social isolation and loneliness (SIL) worsens mortality and other outcomes among older adults as much as smoking. We previously tested the impact of the HOW R U? intervention using peer support from similar-aged volunteers and demonstrated reduced SIL among older adults discharged from the emergency department (ED). Generativity, defined as "the interest in establishing and guiding the next generation," can provide an alternative theoretical basis for reducing SIL via intergenerational programs between members of younger and older generations. The current protocol will examine the impact of younger intergenerational volunteers providing the HOW RU?
METHODS
In this randomized clinical trial, we will compare the following three arms: (1) the standard same-generation peer support HOW R U? intervention, (2) HOW R U? intervention delivered by intergenerational volunteers, and (3) a common wait-list control group. Outcome assessors will be blinded to the intervention. Trained volunteers will deliver 12 weekly telephone support calls. We will recruit participants ≥ 70 years of age with baseline loneliness (six-item De Jong loneliness score of 2 or greater) from two EDs. Research staff will assess SIL, depression, quality of life, functional status, generativity, and perceived benefit at baseline, at 12 weeks, and 24 weeks post-intervention.
DISCUSSION
We hypothesize participants receiving the intergenerational intervention will show improved outcomes compared to the control group and peer support HOW R U?
INTERVENTION
We also hypothesize that participants with higher perceptions of generativity will have greater reductions in SIL than their lower generativity counterparts. Aging is experienced diversely, and social interventions combatting associated SIL should reflect that diversity. As part of a program of research following the Obesity-Related Behavioral Intervention Trials (ORBIT) model, the findings of this RCT will be used to define which intervention characteristics are most effective in reducing SIL.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05998343 Protocol ID:21-0074E. Registered on 24 July 2023.
Topics: Humans; Loneliness; Social Isolation; Aged; Emergency Service, Hospital; Randomized Controlled Trials as Topic; Patient Discharge; Intergenerational Relations; Female; Quality of Life; Male; Peer Group; Social Support; Age Factors; Time Factors; Treatment Outcome; Volunteers
PubMed: 38943176
DOI: 10.1186/s13063-024-08250-2 -
Trials Jun 2024Current management of mesenteric ischemia is primarily endovascular stent treatment. Typical CMI symptoms are postprandial abdominal pain, food fear, weight loss, and... (Comparative Study)
Comparative Study
BACKGROUND
Current management of mesenteric ischemia is primarily endovascular stent treatment. Typical CMI symptoms are postprandial abdominal pain, food fear, weight loss, and diarrhea. Revascularization is often necessary, as mesenteric ischemia may progress to bowel necrosis and death if left untreated. This study aims to compare the outcome using bare metal stent (BMS) or covered stent (CS) in the endovascular treatment of chronic and acute on chronic mesenteric ischemia.
METHODS
This is an investigator-driven, prospective, randomized, single-blinded, and single-center, national cohort study at the Copenhagen University Hospital, Denmark. A total of 98 patients with chronic mesenteric ischemia (CMI) and acute-on-chronic mesenteric ischemia (AoCMI) will be randomized to treatment with either BeSmooth BMS (Bentley Innomed GmbH) or BeGraft CS (Bentley Innomed GmbH). Randomization occurs intraoperatively after lesion crossing.
DISCUSSION
There is currently no published data from prospective controlled trials regarding the preferred type of stent used for the treatment of chronic and acute-on-chronic mesenteric ischemia. This trial will evaluate the short- and long-term outcome of BMS versus CS when treating CMI and AoCMI, as well as the benefit of a more intense postoperative surveillance program.
TRIAL REGISTRATION
ClinicalTrials.gov NCT05244629. Registered on February 8, 2022.
Topics: Humans; Mesenteric Ischemia; Stents; Prospective Studies; Single-Blind Method; Chronic Disease; Denmark; Treatment Outcome; Endovascular Procedures; Randomized Controlled Trials as Topic; Prosthesis Design
PubMed: 38943169
DOI: 10.1186/s13063-024-08285-5