scholarly journals Analysis of Phase 3 telavancin nosocomial pneumonia data excluding patients with severe renal impairment and acute renal failure

2014 ◽  
Vol 69 (4) ◽  
pp. 1119-1126 ◽  
Author(s):  
A. Torres ◽  
E. Rubinstein ◽  
G. R. Corey ◽  
M. E. Stryjewski ◽  
S. L. Barriere
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Renal Impairment ◽  
Nosocomial Pneumonia ◽  
Severe Renal Impairment ◽  
Phase 3

scholarly journals 439. Iclaprim Use for Acute Bacterial Skin and Skin Structure Infection (ABSSSI) is Not Associated with Hyperkalemia: Phase 3 REVIVE Studies

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S218-S218
Author(s):  
David B Huang ◽  
Stephanie S Noviello ◽  
Thomas Lodise ◽  
James McKinnell ◽  
Jamie P Dwyer
Keyword(s):  
Renal Impairment ◽  
Severe Renal Impairment ◽  
Angiotensin Receptor Blockers ◽  
Study Drug ◽  
Angiotensin Converting Enzyme Inhibitors ◽  
Distal Portion ◽  
Phase 3 ◽  
Two Phase ◽  
Double Blind ◽  
Converting Enzyme Inhibitors

Abstract Background Trimethoprim inhibits sodium channels in the distal portion of the renal tubule, thereby impairing renal potassium excretion. Trimethoprim has been associated with a greater risk of hyperkalemia compared with other antibiotics (amoxicillin, nitrofurantoin, cefalexin, ciprofloxacin). An analysis of Phase 3 studies was conducted to determine whether iclaprim, under development for ABSSSI and also a selective bacterial dihydrofolate reductase inhibitor like trimethoprim, is associated with hyperkalemia, relative to vancomycin, an antibiotic not associated with hyperkalemia. Methods A post-hoc safety analysis was conducted on pooled results of two Phase 3, double-blind, randomized (1:1), active-controlled trials (REVIVE-1/-2) in patients with ABSSSI. These trials compared iclaprim 80 mg fixed doses with vancomycin 15 mg/kg; both administered intravenously every 12 hours for 5–14 days. Hyperkalemia was defined as serum potassium (K) ≥5.5 mmol/L, if normal at baseline, while on study drug. Hyperkalemia was compared between treatment groups and stratified subgroup comparisons were performed. Results Demographics and baseline disease characteristics were similar between the pooled iclaprim and vancomycin groups (table). Hyperkalemia occurred during treatment in 1.5% (9/592) and 2.5% (15/599) of patients treated with iclaprim and vancomycin, respectively. Of the patients with hyperkalemia, one patient in each treatment group had moderate to severe renal impairment (creatinine clearance [CrCl] 15–59 mL/minute). Among patients with moderate to severe renal impairment on any RAS, KSD or K supplements, hyperkalemia occurred in 1/16 and 0/16 patients in the iclaprim and vancomycin groups, respectively, and in 2/83 and 0/46 patients with mild to no renal impairment. No patients with hyperkalemia experienced adverse events of palpitations, chest pain, myalgia, muscular weakness or fatigue. Conclusion No differences in hyperkalemia were seen between the iclaprim and vancomycin groups in the Phase 3 REVIVE studies. In general, few cases of hyperkalemia occurred among patients with renal impairment treated with concomitant angiotensin-converting enzyme inhibitors and angiotensin-receptor blockers treated with iclaprim. Disclosures All authors: No reported disclosures.

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

2020 ◽  
Vol 38 (15_suppl) ◽  
pp. e13037-e13037
Author(s):  
Yan Ji ◽  
Vitaly Yartsev ◽  
Yingbo Wang ◽  
Michelle Quinlan ◽  
Paolo Serra ◽  
...  
Keyword(s):  
Renal Function ◽  
Steady State ◽  
Renal Impairment ◽  
Normal Renal Function ◽  
Severe Renal Impairment ◽  
Phase 1 ◽  
Moderate Renal Impairment ◽  
Efficacy And Safety ◽  
Phase 3 ◽  
Integrative Assessment

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.

Recovery of Renal Impairment by Bortezomib-Doxorubicin-Dexamethasone (BDD) in Multiple Myeloma (MM) Patients with Acute Renal Failure. Results from an Ongoing Phase II Study.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 3603-3603 ◽  
Author(s):  
Heinz Ludwig ◽  
Zdenek Adam ◽  
Roman Hajek ◽  
Richard Greil ◽  
Felix Keil ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Renal Impairment ◽  
Treatment Regimen ◽  
Phase Ii ◽  
Response Rate ◽  
De Novo ◽  
Phase Ii Study ◽  
Chronic Hemodialysis ◽  
Ongoing Phase

Abstract Acute renal failure (ARF) is a severe complication of MM often leading to permanent renal dysfunction and dependence on chronic hemodialysis. Reversal of kidney failure can only be achieved by fast and substantial suppression of pathogenic light-chains by effective anti-MM therapy. In a previous pilot study we were able to reverse renal impairment with bortezomib based therapy in 5 of 9 pts (Haematologica 2007). Here, we present preliminary data from an ongoing phase II study in pts with ARF using the BDD regimen. Up to now 37 pts with MM induced ARF (age: median 64 yrs, range 41–82 yrs, DS stage I: 13%, II: 10%, III: 77%; IgGλ: 18%, IgGκ: 23%; Light chainκ: 32%, Light chainλ: 27%) have been enrolled. Seventeen (46%) pts presented with de novo MM, and 20 with progressive disease. ARF was defined as reduction of GFR to <50ml/min due to MM nephropathy in newly diagnosed pts, and as reduction of GFR by >25% and to <60ml/min in pts with previously treated MM and GFR of >60ml/min within the last 4 weeks and with signs of tumor progression. Treatment regimen: Bortezomib 1.0mg/m2, d1,4,8,11, doxorubicin 9mg/m2, d1,4,8,11 until first safety analysis after enrollment of the first 5 pts and thereafter of 9mg2, d1,4, and dexamethasone 40mg d1,4,8,11. Cycles were repeated every 21 days. 22 pts have completed at least 3 cycles and are evaluable for response as yet. Overall response rate was 73% including 8 pts achieving CR, 4 nCR, 4 PR; 3 pts achieved MR. Median GFR at baseline was 17ml/min (range: 4 – 45ml/min) and improved to 45,5 ml/min (range: 11 – 134ml/min). A significant increase in GFR (>75ml/min) was achieved in 9 of the 16 pts with CR-PR while in pts with MR or NC/PD no improvement in GFR was seen. Toxicity was assessed in 25 pts including 3 pts not evaluable for response. Grade 1–2 toxicities (>10% of pts): anemia 40%, neutropenia 23%, thrombopenia 27%, fatigue 50%, infections/fever 64%, neuropathy 36%, edema 32%; diarrhea 27%, nausea 27%, mucositis 23%; Grade 3–4 toxicities: anemia 9%, neutropenia 23%, thrombopenia 9%, infections 18%, neuropathy 1%. Three of the infectious complications were due to herpes virus infections/reactivations. Three pts died during the first treatment cycle; 2 pts from pneumonia (including 1 with sepsis) and 1 pt (age 81 yrs) from myocardial infarction. This led to an adaptation of the treatment regimen including a reduction in the frequency of doxorubicin administration to days 1 and 4 (instead of d1,4,8,11), abandonment of the planned dose increase of bortezomib (to 1.3mg/m2), and addition of mandatory antibacterial and antiviral prophylaxis. In conclusion, overall anti-myeloma response rate in the 22 evaluable pts was 73%, with 12 (54%) pts achieving CR/nCR; ARF could be reverted in 9 pts. (41% of total or 56% of pts. with CR-PR). After dose reduction of the initial regimen, treatment was well tolerated in this high-risk and often multimorbid patient population. Tumor response Number of Pts (evaluable: 22) GFR (ml/min) Baseline Best response CR/nCR 12 18,2 (13–45) 62,5 (20–134) PR 4 25 (15–44) 81 (16–114) MR 3 17 (10–45) 35 (33–45) NC/PD 3 13 (4–15) 18 (11–25) CR-PR 16 GFR >75ml/min: 9 (56%)

Acute renal failure from organophospate poisoning: a case of success with haemofiltration

2003 ◽  
Vol 22 (3) ◽  
pp. 165-167 ◽  
Author(s):  
Moreno Agostini ◽  
Andrea Bianchin
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Mortality Rate ◽  
Renal Impairment ◽  
Distress Syndrome ◽  
Neurological Complications ◽  
Multiple Organ ◽  
Organophosphate Poisoning ◽  
Intentional Ingestion ◽  
Organ Complications

Severe organophosphate poisoning (OPP) has a high mortality rate. Respiratory and neurological complications are common in OPP. Multiple organ distress syndrome (MODS) and renal impairment are relatively rare but correlated with death. In previous publications, in patients who did not survive OPP, their deaths were due to MODS or acute renal failure. A case of intentional ingestion of an organophosphate with renal and multiple organ complications is described. In addition to the standard atropine/oxime regimen, continuous venous-venous haemofiltration (CVVH) therapy was started; the patient survived this intoxication. The pathogenesis of renal injury by OPP is unclear and more insight is required. In our experience, CVVH can be a valid therapy, considering in particular the toxicokinetics of the organophosphate.

scholarly journals Considerations in the Selection of Renal Dosage Adjustments for Patients with Serious Infections and Lessons Learned from the Development of Ceftazidime-Avibactam

2020 ◽  
Vol 64 (4) ◽  
Author(s):  
Jianguo Li ◽  
Mark Lovern ◽  
Todd Riccobene ◽  
Timothy J. Carrothers ◽  
Paul Newell ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Severe Renal Impairment ◽  
Complicated Urinary Tract Infection ◽  
Development Program ◽  
Lessons Learned ◽  
Total Daily Dose ◽  
Population Pharmacokinetic ◽  
Phase 3 ◽  
Two Phase

ABSTRACT An extensive clinical development program (comprising two phase 2 and five phase 3 trials) has demonstrated the efficacy and safety of ceftazidime-avibactam in the treatment of adults with complicated intra-abdominal infection (cIAI), complicated urinary tract infection (cUTI), and hospital-acquired pneumonia (HAP), including ventilator-associated pneumonia (VAP). During the phase 3 clinical program, updated population pharmacokinetic (PK) modeling and Monte Carlo simulations using clinical PK data supported modified ceftazidime-avibactam dosage adjustments for patients with moderate or severe renal impairment (comprising a 50% increase in total daily dose compared with the original dosage adjustments) to reduce the risk of subtherapeutic drug exposures in the event of rapidly improving renal function. The modified dosage adjustments were included in the ceftazidime-avibactam labeling information at the time of initial approval and were subsequently evaluated in the final phase 3 trial (in patients with HAP, including VAP), providing supportive data for the approved U.S. and European ceftazidime-avibactam dosage regimens across renal function categories. This review describes the analyses supporting the ceftazidime-avibactam dosage adjustments for renal impairment and discusses the wider implications and benefits of using modeling and simulation to support dosage regimen optimization based on emerging clinical evidence.

scholarly journals 2227. Outcomes in Patients with Renal Impairment from a Phase 3 Clinical Trial for Ceftolozane–Tazobactam (C/T) Treatment of Nosocomial Pneumonia (ASPECT-NP)

2019 ◽  
Vol 6 (Supplement_2) ◽  
pp. S760-S761
Author(s):  
Jennifer A Huntington ◽  
Brian Yu ◽  
Linping Li ◽  
Erin Jensen ◽  
Christopher Bruno ◽  
...  
Keyword(s):  
Renal Function ◽  
Renal Impairment ◽  
Nosocomial Pneumonia ◽  
Clinical Cure ◽  
Study Drug ◽  
Double Blind Study ◽  
Phase 3 ◽  
Double Blind ◽  
Intent To Treat ◽  
Cure Rates

Abstract Background ASPECT-NP, a phase 3, randomized, double-blind study, evaluated C/T (at double the approved dose for other indications) vs. meropenem (MEM) in adults with ventilated nosocomial pneumonia. We compared safety and efficacy outcomes from this trial among patients with and without renal impairment (RI). Methods Patients were stratified by age and diagnosis and were randomized 1:1 to intravenous (IV) C/T 3 g every 8 h or IV MEM 1 g every 8 h. Study drug was administered for 8–14 days; doses were adjusted for moderate and severe RI. Eligible patients were mechanically ventilated; those on renal replacement therapy or with creatinine clearance (CrCL) < 15 mL/minute were excluded. Key efficacy endpoints included clinical cure rates at the test of cure (TOC) visit in the intent-to-treat (ITT) and clinically evaluable (CE) populations and Day 28 all-cause mortality (ACM) in the ITT population. In this analysis, patients were stratified based on renal function for outcome comparisons: normal renal function (CrCL ≥ 80 mL/minute); mild RI (CrCL > 50 to < 80 mL/minute); moderate RI (CrCL ≥ 30 to ≤ 50 mL/minute); and severe RI (CrCL ≥ 15 to < 30 mL/minute). Results A total of 726 patients were enrolled (C/T, N = 362; MEM, N = 364). Clinical cure rates at the TOC visit (CE and ITT populations) were robust across CrCL subgroups in both treatment arms and were similar based on 95% confidence intervals for treatment differences that included 0 (table). Day 28 ACM rates for patients with moderate and severe RI were numerically higher than those with mild RI in the MEM treatment arm. Rates of treatment-emergent adverse events (TEAEs) were similar in both treatment arms and across CrCL subgroups, with rates generally increasing with increasing RI severity. Rates of treatment-related TEAEs were low across treatment arms and CrCL subgroups with no treatment-related deaths reported. Conclusion Similar clinical cure and Day 28 ACM rates at the TOC visit were found across treatment groups for all CrCL subgroups, consistent with the overall primary and key secondary efficacy results for the ASPECT-NP study. Both drugs were well-tolerated. The results of this analysis indicate that the use of dose-adjusted C/T is appropriate in patients with nosocomial pneumonia and moderate or severe RI. Disclosures All authors: No reported disclosures.

scholarly journals Prolonged Hypercalcemia After Recovery From Severe Rhabdomyolysis and Acute Renal Failure

2021 ◽  
Vol 5 (Supplement_1) ◽  
pp. A216-A216
Author(s):  
Tanvisha Mody ◽  
Jamie Mullally
Keyword(s):  
Renal Failure ◽  
Creatine Kinase ◽  
Renal Function ◽  
Acute Renal Failure ◽  
Renal Impairment ◽  
Recovery Phase ◽  
Urinary Calcium ◽  
Calcium Excretion ◽  
Vitamin D Levels ◽  
Electrolyte Abnormalities

Abstract Introduction: Rhabdomyolysis is characterized by elevated creatine kinase, electrolyte abnormalities and acute renal failure. After the initial hypocalcemic phase, serum calcium levels can normalize or become significantly elevated during the recovery phase. We report a case of persistent hypercalcemia during the recovery phase of rhabdomyolysis-induced acute renal failure. Case Description: A 26-year old woman with Cornelia de Lange syndrome initially presented with septic shock, complicated by severe rhabdomyolysis and acute renal failure requiring hemodialysis. On admission, creatine kinase level was &gt;30,500 U/L [29–168], BUN 95 mg/dL [6–22], Creatinine 3.39 mg/dL [0.57–1.11], and Corrected Calcium 7.1 mg/dL [8.6–10.2]. Approximately 1 month after admission, the patient developed hypercalcemia with corrected calcium values ranging from 10.4 to 14.5 mg/dL with PTH 10.5 pg/mL [8.7–77.1] and 1,25-Dihydroxyvitamin D and 25-OH Vitamin D levels &lt;8.0 pg/dL [18–78] and 21.20 ng/mL [30–80], respectively. Her renal function improved and dialysis was discontinued seven weeks after initial presentation, although her GFR remained impaired (22 mL/min/BSA). She remained hypercalcemic and was treated with intermittent doses of Calcitonin when the level rose above 12.0 mg/dL. Spot urinary calcium to creatinine ratio was low at 0.13. Improvement in her calcium was seen with a level of 10.8 mg/dL eleven weeks after she was initially noted to be hypercalcemic and she was able to be discharged. Two weeks after discharge, an outpatient calcium improved further to 10.4 mg/dL. Discussion: Rhabdomyolysis is a clinical syndrome that results from severe muscle damage with release of the breakdown products from injured muscle cells leading to acute renal failure and electrolyte abnormalities. The initial hypocalcemic phase is due to entry of calcium into damaged myocytes and deposition of calcium salts in damaged muscle. After recovery, most patients have normalization of calcium levels. However, in up to one-third of patients, a rebound hypercalcemia can ensue. The proposed mechanism is massive muscle calcium release during renal recovery. In the cases reported, the hypercalcemia phase resolves by an average of 8 days with the longest reported recovery being 3.5 months. We report a case of prolonged hypercalcemia in the setting of continued renal impairment. It appears that the patient’s low GFR impaired urinary calcium excretion resulting in persistent hypercalcemia which eventually resolved over time with some improvement in renal function. Other case reports have described treatment with IV fluids, Calcitonin, Pamidronate and hemodialysis, although the efficacy of these interventions is unclear. Rhabdomyolysis is an under-recognized cause of hypercalcemia. Our case highlights the potential for prolonged hypercalcemia after recovery from rhabdomyolysis in the setting of renal impairment.

scholarly journals A Stepwise Diagnosis of Sarcoidosis Presenting with Renal Impairment and Hypercalcemia

2015 ◽  
Vol 12 (1) ◽  
pp. 56-61
Author(s):  
Alper Alp ◽  
Hakan Akdam ◽  
Ibrahim Meteoglu ◽  
Emel Ceylan ◽  
Arzu Cengiz ◽  
...  
Keyword(s):  
Renal Failure ◽  
Acute Renal Failure ◽  
Renal Impairment ◽  
Renal Disease ◽  
Clinical Presentation ◽  
Renal Involvement ◽  
Granulomatous Disease ◽  
Organ Function ◽  
Immune Mediated ◽  
Clinical Conditions

Abstract Sarcoidosis is a multisystem, immune-mediated, granulomatous disease. Clinical presentation of this disease may vary; in majority of cases (~90%) thoracic involvement is the leading sign. Although renal involvement is thought to be uncommon in sarcoidosis this entity may not be so rare. Hypercalcemia seems to be the most likely cause of sarcoidosis-associated renal disease, it can even cause acute renal failure in 1-2% of sarciodosis patients. Immediate treatment is appropriate whenever organ function is threatened or when symptoms are severe. We present a case of sarcoidosis with hypercalcemia excluding other clinical conditions, which may potentially confuse the diagnosis.

Suspected Nafcillin-Induced Interstitial Nephritis

1993 ◽  
Vol 27 (2) ◽  
pp. 170-173 ◽  
Author(s):  
Sudip Roy Guharoy ◽  
Sheila Kar ◽  
James Mcgalliard
Keyword(s):  
Renal Failure ◽  
Renal Function ◽  
Acute Renal Failure ◽  
Case Report ◽  
Literature Review ◽  
Renal Impairment ◽  
Interstitial Nephritis ◽  
Acute Interstitial Nephritis ◽  
Staphylococcal Pneumonia ◽  
Allergic Manifestations

Objective To present a case of nafcillin-induced interstitial nephritis. Methodology Case report and literature review. Setting Hospital. Results Three days following initiation of nafcillin therapy for staphylococcal pneumonia, an 80-year-old woman developed allergic manifestations and progressive renal impairment suggestive of acute allergic interstitial nephritis. These manifestations were completely reversed within 96 hours of cessation of nafcillin therapy. Conclusions In the clinical setting of acute renal failure in a patient on nafcillin therapy, acute interstitial nephritis should be considered. Prompt cessation of nafcillin therapy has generally been associated with reversal of symptoms and an improvement in renal function.

Sign in / Sign up

Export Citation Format

Share Document