Safety and efficacy of sodium picosulfate, magnesium oxide, and citric acid bowel preparation in patients with baseline renal impairment or diabetes: subanalysis of a randomized, controlled trial

Background: Selecting a bowel preparation for patients with renal impairment or diabetes requires special consideration. We aimed to describe the effect of baseline renal impairment or diabetes on the safety, efficacy, and tolerability of low-volume sodium picosulfate, magnesium oxide, and citric acid (SPMC) ready-to-drink oral solution bowel preparation. Methods: A post hoc secondary analysis was performed from a randomized, assessor-blinded study of SPMC oral solution bowel preparation in participants with mild or moderate baseline renal impairment or diabetes. Primary efficacy endpoint (‘responders’) was the proportion of participants with ‘excellent’ or ‘good’ ratings on a modified Aronchick Scale (AS). Secondary efficacy outcomes were the quality of ascending colon cleansing from the Boston Bowel Preparation Scale (BBPS), and selected results from the Mayo Clinic Bowel Prep Tolerability Questionnaire. Safety assessments included adverse events (AEs), adenoma detection, and laboratory evaluations. Results: Similar overall colon cleansing was demonstrated in the subgroups, with >85% of participants in any subgroup rated as responders by the AS, and >92% of participant responders by the BBPS. Most participants reported a tolerable bowel preparation, regardless of baseline renal impairment or diabetes history. Safety of SPMC oral solution was similar between all subgroups and the overall cohort. For the mild renal impairment, moderate renal impairment, and diabetes subgroups, respectively, commonly reported, drug-related AEs were nausea (2.6%, 5.3%, 1.4%) and headache (2.2%, 2.6%, 4.3%). Conclusions: Ready-to-drink SPMC oral solution demonstrated efficacious colon cleansing in patients with baseline mild/moderate renal impairment or diabetes, with a tolerable bowel preparation reported by most. Clinical Trial Registration: ClinicalTrials.gov identifier: NCT03017235

Abstract 15192: Effectiveness and Safety of Reduced Dose of Dabigatran for High Bleeding Risk Patient Subgroups With Atrial Fibrillation

Off-label reduced dosing of direct oral anticoagulants is common among patients at high bleeding risk with atrial fibrillation (AF), however, outcomes data of reduced dosing are limited. We evaluated the effectiveness and safety of reduced dose of dabigatran [110 mg twice daily (BID)] vs. standard dose [150 mg BID] in high bleeding risk subgroups with AF. We identified adult patients with AF who initiated dabigatran (index date) with creatinine clearance (CrCl) ≥30 mL/min between 2012-2018 from Kaiser Permanente Southern California. Three high bleeding risk subgroups were identified: 1) patients aged ≥80 years; 2) patients with moderate renal impairment (CrCl 30-49 mL/min) regardless of age; or 3) patients with bleeding within 12 months prior to the index date or HAS-BLED score ≥3. Patients were followed through December 2018 for stroke or systemic embolism, major bleeding requiring hospitalization, and all-cause mortality. Cause-specific hazard regression models were used to investigate associations between dabigatran dose and clinical outcomes adjusting for covariates and considering competing risks of death. Among high bleeding risk patients with AF [3,749 aged ≥80 years; 1,716 with moderate renal impairment; 3,051 with recent bleed or high HAS-BLED score], 34% received reduced dose of dabigatran. Patients who received reduced dose were older, had reduced renal function, and had more comorbidities. Compared with standard dose, reduced dose of dabigatran was not associated with an increased risk of stroke or systemic embolism but was associated with lower risk of major bleed in patients aged ≥80 years ( Table ). Reduced dose of dabigatran was also associated with lower risk of mortality among patients aged ≥80 years and patients with moderate renal impairment. A lower risk of bleeds and mortality associated with reduced vs standard dose of dabigatran in high-risk patients with AF suggest a better dosing strategy for these risk groups.

Profile of patients diagnosed with acute venous thromboembolism in routine practice according to age and renal function: RE-COVERY DVT/PE study

In randomized clinical trials (RCTs) of nonvitamin K antagonist oral anticoagulants (NOACs) for acute venous thromboembolism (VTE), ~ 12–13% of patients were elderly and ~ 26% had mild-to-moderate renal impairment. Observational studies are not restricted by the selection and treatment criteria of RCTs. In this ancillary analysis of the RE-COVERY DVT/PE global observational study, we aimed to describe patient characteristics, comorbidities, and anticoagulant therapy for subgroups of age (< or ≥ 75 years) and renal impairment (creatinine clearance [CrCl; estimated with Cockcroft–Gault formula] < 30 [severe], 30 to < 50 [moderate], 50 to < 80 [mild], ≥ 80 [normal] mL/min). Of 6095 eligible patients, 25.3% were aged ≥ 75 years; 38.2% (1605/4203 with CrCl values) had mild-to-moderate renal impairment. Comorbidities were more common in older patients (73.9% aged ≥ 75 vs. 58.1% < 75 years) and in those with mild or moderate versus no renal impairment (75.9%, 80.9%, and 59.3%, respectively). At hospital discharge or 14 days after diagnosis (whichever was later), most patients (53.7% and 55.1%, respectively) in both age groups received NOACs; 20.8% and 23.4%, respectively, received vitamin K antagonists, 19.0% and 21.8% parenteral therapy, 2.3% and 3.8% other anticoagulant treatments. Use of NOACs decreased with worsening renal impairment (none 58.5%, moderate 49.6%, severe 25.7%) and, in younger versus older patients with moderate renal impairment (33.1% vs. 56.1%). In routine practice, there are more elderly and renally impaired patients with VTE than represented in RCTs. Decreasing renal function, but not older age, was associated with less NOAC use. Clinical Trial Registration: http://www.clinicaltrials.gov. Unique identifier: NCT02596230. Graphic abstract Decreasing renal function, particularly in the subgroup with CrCl < 30 mL/min, but not older age, was associated with less use of nonvitamin K antagonist oral anticoagulants (NOACs). Nevertheless, more than half of the older patients with moderate renal impairment received a NOAC as their oral anticoagulant.

Integrative assessment of the effect of renal function on ribociclib treatment and dose recommendation in advanced breast cancer patients.

e13037 Background: Ribociclib is an orally administered CDK4/6 inhibitor used in combination with endocrine therapy (ET) to treat women with hormone receptor-positive (HR+), human epidermal growth factor receptor-2–negative advanced breast cancer (ABC). An integrative assessment was conducted to evaluate the effect of renal function on the pharmacokinetics (PK), efficacy and safety of ribociclib. Methods: To assess the effect of mild and moderate renal impairment, a subgroup analysis was performed to evaluate PK parameters of ribociclib following oral administration of 600 mg QD 3 weeks on/1 week off in two Phase 1/2 and one Phase 3 clinical trials. Steady-state PK exposures in ABC patients at the 600 mg dose was estimated by a population PK model developed based on a pooled dataset from five Phase 1 to 3 trials and were compared by renal function. Efficacy and safety were also analyzed by renal function in a Phase 2 and three Phase 3 trials in ABC patients. The effect of severe renal impairment on ribociclib PK was assessed in a Phase I study in non-cancer subjects following a single oral 400 mg dose. Results: PK analyses in cancer patients showed that both single-dose and steady-state exposure of ribociclib at the 600 mg dose in patients with mild or moderate renal impairment were comparable to patients with normal renal function. Estimated steady-state PK exposure in patients with mild or moderate renal impairment is also comparable to patients with normal renal function. The primary efficacy results of progression free survival (PFS) and the safety profiles were comparable across renal-function cohorts in ABC patients. In non-cancer subjects administered a single oral dose of 400 mg, ribociclib AUCinf and Cmax increased 2.67- and 2.30-fold in subjects with severe renal impairment, respectively, compared to subjects with normal renal function. Conclusions: PK, efficacy and safety of ribociclib are consistent across patients with normal renal function, mild or moderate renal impairment. Hence, no dose adjustment is required in mild or moderate renal impaired patients. Severe renal impaired patients are recommended to have a reduced dose based on PK data in non-cancer subjects.