This study aims to determine if GLP1RA is safe and tolerable in maintenance dialysis population, adherence, and feasibility of a larger definitive cardiovascular outcome trial in this population. Participants will be randomized 1:1 to either weekly subcutaneous semaglutide versus usual care and followed for 26 weeks.
In this randomized pilot study, Individuals randomized to the active intervention arm will take semaglutide once weekly. Semaglutide (injectable, 1.34 mg/mL) is delivered subcutaneously via a multiple-use pen-injector that can be used to dial in all required doses on the same pen-injector. The clinical pen has a drum scale of 1-80 in increments of 1. Participants will be trained/re-trained on injector use at 0, 4, 8, and 12 weeks. For participants receiving in-centre hemodialysis, the intervention may be administered during the dialysis session by nursing personnel. Semaglutide will be titrated using an algorithm used in previous trials with a starting dose of 0.25 mg/week, with an increase to 0.5 mg/week after 4 weeks, and to the maximum dose of 1.0 mg/week after 8 weeks as tolerated. If a participant experiences an adverse effect, efforts will be made to maintain the current dosage, with dose reductions or treatment pauses permitted at the discretion of the site investigator. Patient receiving concomitant insulin therapy will have therapy adjusted as per a pre-specified algorithm. Participants allocated to the usual care arm will receive usual care. Primary outcomes: 1. Feasibility of study recruitment: ≥ 40% of fully eligible patients consent to participate in the trial. 2. Adherence to intervention: ≥ 70% of enrolled patients are adherent to the study intervention over the 26-week follow-up period. 3. Ability to follow: ≥ 90% of participants will be successfully followed to week Secondary outcomes: * Proportion Discontinuing Intervention * Safety Events * Major Adverse Cardiovascular Outcomes (Cardiovascular death, non-fatal myocardial infarction, non-fatal stroke, or a peripheral arterial event) * Body Weight/BMI * Systolic/diastolic blood pressure * Insulin dosage, glycemic control (HbA1c and random glucose) * Lipid profile * Hemoglobin, Calcium, Phosphate, PTH * EQ-5D-5L for baseline-adjusted changes in quality of life and symptom burden
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
TREATMENT
Masking
NONE
Enrollment
100
Individuals randomized to this arm will take semaglutide once weekly. For participants receiving in-centre hemodialysis, the intervention may be administered during the dialysis session by nursing personnel based on the patient's preference.
Unity Health Toronto
Toronto, Ontario, Canada
Adherence of Study Intervention
This will be determined if ≥ 70% of enrolled number of eligible participants (who are randomized) are adherent to the study intervention over the 26-week follow-up period.
Time frame: 26 weeks
Study Medication Discontinuation
To determine the proportions of enrolled number of participants who permanently discontinue the study medication in the semaglutide arm.
Time frame: 26 weeks
Feasibility of Study Recruitment
This will be determined if ≥ 40% of the number of fully eligible participants (potential participants who were screened and identified to meet inclusion/exclusion criteria) consent to participate in the trial.
Time frame: 26 weeks
Safety Events of Special Interest
To identify safety events of special interest such as gastrointestinal symptoms, acute biliary disease, acute pancreatitis, interventions for diabetic retinopathy, heart failure exacerbations, malignant neoplasms, and the number of hypoglycemic events.
Time frame: 26 weeks
Major Adverse Cardiovascular Events
This is a composite of CV death, non-fatal myocardial infarction, non-fatal stroke, or a peripheral arterial event.
Time frame: 26 weeks
Follow Up Percentage at 26 weeks
To determine if ≥ 90% of participants (who are enrolled) will be successfully followed to week 26 (end of study participation).
Time frame: 26 weeks
Patient Reported Measures
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The validated EuroQol-5 Dimensions-5 Levels (EQ-5D-5L) score will be used to evaluate baseline-adjusted changes in quality of life and symptom burden. The EQ-5D-5L asks individuals to rate their overall health on a visual scale from 0 to 100, where 0 represents the worst imaginable health and 100 represents the best imaginable health.
Time frame: 26 weeks