MO559ASCEND-ND: STUDY DESIGN AND BASELINE CHARACTERISTICS

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Vlado Perkovic ◽  
Allison Blackorby ◽  
Borut Cizman ◽  
Kevin Carroll ◽  
Alexander Cobitz ◽  
...  
Keyword(s):  
Serum Ferritin ◽  
Darbepoetin Alfa ◽  
Trial Design ◽  
Rescue Therapy ◽  
Transferrin Saturation ◽  
Statistical Testing ◽  
Efficacy And Safety ◽  
Primary Endpoints ◽  
History Of ◽  
Baseline Characteristics

Abstract Background and Aims The Anemia Study in Chronic kidney disease (CKD): Erythropoiesis via a Novel prolyl hydroxylase inhibitor (PHI) Daprodustat-Non-Dialysis (ASCEND-ND; NCT02876835) trial is evaluating the efficacy and safety of daprodustat when compared with darbepoetin alfa in CKD patients with anaemia not requiring dialysis. We report the trial design as well as key baseline characteristics of participants. Method Eligible patients from 39 countries were adults with CKD stages 3–5 who were able to provide informed consent and demonstrated adherence to daprodustat placebo tablets and study procedures during the run-in period. Patients were eligible if (1) they were not using erythropoiesis stimulating agents (ESAs) and had a screening haemoglobin (Hb) 8 to 10 g/dL or if (2) they were receiving ESAs with screening Hb of 8 to 12 g/dL. Patients were required to be iron replete [transferrin saturation (TSAT) >20% and serum ferritin >100 ng/mL] at screening. Participants were randomised to daprodustat or darbepoetin alfa (1:1) in an open-label (sponsor-blind) trial design with blinded endpoint assessment. An IDMC conducts regular reviews of unblinded safety and efficacy data and makes recommendations for additions or adjustments. An external, independent and blinded Clinical Events Classification (CEC) group, led by the Duke Clinical Research Institute, in collaboration with George Clinical, adjudicate predefined events. During the study, both groups had randomised treatment adjusted using a protocol-defined algorithm targeting a Hb range of 10 to 11 g/dL. Participants also followed protocol-defined iron management criteria to ensure they remained iron replete. Additionally, an anaemia rescue algorithm was in place to minimise the risk of extended periods of inadequate Hb response and to ensure consistent application of rescue therapy across the study. The co-primary endpoints are mean change in Hb between baseline and Evaluation Period (EP; Weeks 28 to 52, inclusive) and time to first adjudicated major adverse cardiovascular event (MACE; composite of all-cause mortality, non-fatal myocardial infarction, and non-fatal stroke). The study has more than 99% power for the Hb non-inferiority (NI) test with an NI margin of -0.75 g/dL for the treatment difference of mean change in Hb between baseline and EP, and approximately 90% power to exclude the NI margin of 1.25 for time to first adjudicated MACE, for daprodustat compared with darbepoetin alfa. Conditional on both co-primary endpoints achieving NI at the one-sided 2.5% level, statistical testing will progress to evaluate MACE and the principal secondary endpoint of CKD progression for superiority. These tests will be multiplicity adjusted. Results A total of 3872 patients were randomised (median age 67 years, 56% female; 55% white, 28% Asian, and 10% black). The median baseline Hb was 9.8 g/dL, serum ferritin was 274 ng/mL, TSAT 30%, and eGFR 18 mL/min/1.73 m2. Among randomised patients, 54% were ESA non-users, 57% reported a history of diabetes mellitus and 36% a history of cardiovascular disease. Median blood pressure was 135/74 mmHg. Sixty percent of participants were taking angiotensin converting enzyme inhibitors or angiotensin II receptor blockers, while 57% were taking lipid modifying agents at baseline. The trial is expected to complete during 2021. Conclusion ASCEND-ND will define the efficacy and safety of daprodustat compared with darbepoetin alfa in the treatment of patients with anaemia associated with CKD not requiring dialysis.

Intravenous (IV) Iron Supplementation in Patients with Chemotherapy-Induced Anemia (CIA) Receiving Darbepoetin alfa Every 3 Weeks (Q3W): Iron Parameters in a Randomized Controlled Trial.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1552-1552 ◽  
Author(s):  
Christian Lerchenmueller ◽  
Faress Husseini ◽  
Bernd Gaede ◽  
Tony Mossman ◽  
Tamas Suto ◽  
...  
Keyword(s):  
Serum Ferritin ◽  
Darbepoetin Alfa ◽  
Iron Supplementation ◽  
Transferrin Saturation ◽  
Oral Iron ◽  
Ferritin Concentration ◽  
Standard Practice ◽  
Serum Ferritin Concentration ◽  
Iv Iron ◽  
Iron Parameters

Abstract Background and Aim: The role of IV iron supplementation during treatment with erythropoiesis-stimulating agents (ESAs) in patients with CIA is of increasing interest as a possible means of improving response. This randomized, open-label, multicenter study was designed to evaluate the safety and efficacy of IV iron vs standard practice in CIA patients receiving darbepoetin alfa. Interim efficacy analyses showed a higher response rate for darbepoetin alfa with IV iron compared to darbepoetin alfa with standard iron practice with no difference in the safety profile between the treatment arms (Vanderbroek et al, EHA 2006). Iron parameters are reported here. Methods: Eligible patients were diagnosed with a non-myeloid malignancy and had CIA with a baseline hemoglobin (Hb) value < 11g/dL. All patients received darbepoetin alfa 500 mcg administered Q3W with the SureClick™ prefilled autoinjector. Patients were randomized 1:1 to IV iron 200 mg (single dose Q3W at the same time as darbepoetin alfa or in 2 doses of 100 mg within 3 weeks) or standard practice (oral iron or no iron). Randomization was stratified by tumor type and baseline Hb category (< 10 or ≥10 g/dL). Results: A total of 400 patients were randomized. Mean (SD) age of the study population was 61.4 (11.5) years; range, 20–86. Sixty percent (n=241) of participants were women; 28% (n=114) had lung or gynecological tumors; and 52% (n=208) had a baseline Hb value ≥10 g/dL. In the interim analysis population (n=196), the mean (SD) weekly dose of IV iron was 64.8 (6.6) mg in the IV iron group (n=100). In the standard practice group, 28 of 96 patients (29%) received oral iron and 2 (2%) received IV iron (these patients were analyzed as randomized). Mean (standard error) serum ferritin concentrations and percent transferrin saturation (TSAT) in the 2 groups from baseline (BL) to end of study (EOS) are shown in the figure. Conclusions: The combination of darbepoetin alfa Q3W and IV iron appeared to be associated with a trend toward increased mean serum ferritin levels compared to the standard practice control arm. In contrast, mean TSAT surprisingly appeared to be similar in the 2 groups for most of the study period, perhaps suggesting that TSAT is influenced by other factors. Iron management appears to be an important factor in the response to ESAs and the findings presented here suggest the need for additional exploration into iron uptake and demand in cancer patients treated with darbepoetin alfa. Serum Ferritin Concentration Serum Ferritin Concentration Transferrin Saturation (%) Transferrin Saturation (%)

A Randomized Phase II Study Evaluating the Efficacy and Safety of Deferasirox Versus Deferoxamine in Patients with Sickle Cell Disease (SCD): 2-Year Results Including Pharmacokinetics (PK) and Safety of Deferasirox with Concomitant Hydroxyurea Therapy

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 1082-1082 ◽  
Author(s):  
Elliott Vichinsky ◽  
Marcela Torres ◽  
Jonathan Glass ◽  
Caterina P Minniti ◽  
Stéphane Barrette ◽  
...  
Keyword(s):  
Liver Function ◽  
Serum Creatinine ◽  
Sickle Cell ◽  
Serum Ferritin ◽  
Safety Data ◽  
Efficacy And Safety ◽  
Post Dose ◽  
Safety And Efficacy ◽  
History Of

Abstract Abstract 1082 Background: Long-term efficacy and safety of the iron chelator deferasirox in SCD patients has been previously reported (Vichinsky et al. BJH 2011). Hydroxyurea (HU), a common treatment for SCD, is associated with adverse events (AEs) such as bone marrow depression. However, long-term data for iron chelation and concomitant HU are limited. This study provides further efficacy and safety data for deferasirox including PK and safety data + HU. Methods: SCD patients aged ≥2 yrs and iron overload from blood transfusions were enrolled and randomized 2:1 to deferasirox (DFX; 20 mg/kg/day) or deferoxamine (DFO; 175 mg/kg/week [wk]) for 24 wks (24-wk DFX or DFO cohort). DFO patients then crossed over to DFX; all patients received DFX up to Wk 52. Patients entered a 52-wk extension receiving DFX (DFX up to 2 yrs cohort). PK sampling was carried out pre- and 2 hrs post-dose in patients on DFX at Wk 12. Plasma concentrations of DFX and iron-complex Fe-[DFX]2 were determined using a validated LC-MS/MS method. Dose adjustments were implemented for changes in patient weight, serum ferritin, serum creatinine, liver function tests and rash. Primary objective was DFX safety compared with DFO during 24 wks. Secondary objectives included DFX safety and efficacy for up to 2 yrs and DFX safety in patients with concomitant HU. Results: 24-weeks, DFX (n=135) vs DFO (n=68). Patients were severely iron overloaded at baseline (BL); 37% had serum ferritin ≥4000 ng/mL (median 3385 ng/mL). In the DFX and DFO cohorts, respectively, 93 and 78% of patients completed 24 wks of treatment. AEs leading to discontinuation were reported by 0 and 1 (1.8%) patient in the DFX and DFO cohorts, respectively. Investigator-assessed drug-related AEs were reported in 27 and 29% of patients in the DFX vs DFO cohort, respectively; most common (>5%) were gastrointestinal (DFX vs DFO cohort: diarrhea 10.4 vs 3.6%; nausea 5.2 vs 3.6%). Serious AEs (any causality) were reported in 30 and 36% of patients in the DFX vs DFO cohort, respectively. One death occurred in the DFX cohort, not considered drug-related (patient had past history of multi-organ failure). At the 3–6 month timepoint, median change from BL in serum ferritin was –196 (range –4029 to 10,168) and –400 (range –10,001 to 3908) ng/mL for DFX (n=130) and DFO (n=58) cohorts, respectively. Up to 2 years DFX (n=188). 135 (72%) patients who received DFX completed the study; 5 (3%) patients discontinued due to AEs. Average actual dose was 21.2 ± 3.6 mg/kg/day. Most common investigator-assessed drug-related AEs (>5%) were diarrhea (11.7%), nausea (6.9%) and abdominal pain (5.3%). Drug-related serious AEs were reported in 8 (4.3%) patients; most common were increased aspartate aminotransferase (AST) and abnormal liver function test (n=2, for each). One additional death occurred; not considered drug-related (patient had history of congestive heart failure with worsening pulmonary hypertension). 4 patients had 2 consecutive serum creatinine increases >33% above BL and >upper limit of normal; increases were transient and resolved with dose adjustment or temporary interruption. Mean ± SE change from BL in serum ferritin (per-protocol, adjusted for amount of transfused blood) was –683 ± 205 ng/mL (n=87). PK, safety and efficacy of DFX + HU (n=28) and DFX (n=160). Mean DFX concentration (μmol/L) pre- and 2-hr post-dose were similar in patients receiving DFX + HU (n=14) vs DFX (n=81); pre-dose 13.3 vs 19.8, post-dose 74.2 vs 79.4. Mean Fe-[DFX]2 concentration (μmol/L) pre- and post-dose was similar in patients receiving DFX + HU (n=14) vs DFX (n=85); pre-dose 0.9 vs 0.6, post-dose 1.9 vs 1.7. One of 5 patients discontinuing DFX due to AEs was receiving concomitant HU. Overall the type and incidence of AEs in patients receiving DFX + HU vs DFX were similar (Table). At the 21–24 month time-point, mean change in serum ferritin was –593 ng/mL (n=15) and –721 ng/mL (n=81) for DFX + HU vs DFX cohorts, respectively. Conclusions: Consistent with previous studies, this study confirms that deferasirox has a clinically manageable safety profile, and is comparable overall with DFO in SCD patients, with many AEs related to the underlying condition (eg, sickle cell anemia with crisis, pyrexia, infections). This study confirms the long-term efficacy of deferasirox with clinically meaningful reductions in serum ferritin over 2 years. PK, efficacy and overall safety of deferasirox were not influenced by concomitant HU. Disclosures: Vichinsky: Novartis: Honoraria, Research Funding. Habr:Novartis: Employment. Lynch:Novartis: Employment. Zhang:Novartis: Employment. Files:Novartis: Speakers Bureau; Medical University of South Carolina: Research contract agreement.

scholarly journals FC 073REGIONAL EFFICACY AND SAFETY RESULTS OF ROXADUSTAT COMPARED WITH PLACEBO OR DARBEPOETIN ALFA IN NON-DIALYSIS-DEPENDENT (NDD) CHRONIC KIDNEY DISEASE (CKD) PATIENTS WITH ANAEMIA

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Nada Dimkovic ◽  
Ciro Esposito ◽  
Jonathan Barratt ◽  
Christophe Mariat ◽  
Evgeny Shutov ◽  
...  
Keyword(s):  
Eastern Europe ◽  
Darbepoetin Alfa ◽  
Western Europe ◽  
Rescue Therapy ◽  
Regional Analysis ◽  
Controlled Study ◽  
Efficacy And Safety ◽  
Central Eastern Europe ◽  
Central Eastern ◽  
Rbc Transfusion

Abstract Background and Aims Roxadustat regulates erythropoiesis and iron metabolism through hypoxia-inducible factor prolyl hydroxylase inhibition. This regional analysis evaluated efficacy and safety for roxadustat versus placebo/darbepoetin alfa (DA) in NDD CKD patients with anaemia. Method Results from three, double-blind phase 3 studies comparing roxadustat to placebo (ALPS, ANDES, OLYMPUS) in patients with anaemia and stage 3-5 NDD CKD were pooled and evaluated alongside results of an open-label study comparing roxadustat to DA (DOLOMITES) in the same population. Efficacy outcomes were compared in three regions (Europe, US, and other) in placebo-controlled studies (PCS) and two regions (Western Europe/Israel and Central/Eastern Europe) in the DA-controlled study (DCS). The primary efficacy endpoint in Europe was haemoglobin (Hb) response, defined as Hb ≥11.0 g/dL that changed from baseline (CFB) by ≥1.0 g/dL in patients with Hb &gt;8.0 g/dL or as CFB ≥2.0 g/dL in patients with Hb ≤8.0 g/dL. The secondary efficacy endpoint was Hb CFB to Weeks 28-36 without rescue therapy (intravenous iron, red blood cell [RBC] transfusion, or erythropoiesis-stimulating agent [ESA] for PCS; RBC transfusion or ESA [roxadustat only] for DCS). Incidence of treatment-emergent adverse events (TEAEs) was summarised descriptively in two regions in PCS (Europe and non-Europe) and two regions in DCS (Western Europe/Israel and Central/Eastern Europe). Results A total of 4886 patients were randomised (2709 roxadustat; 1884 placebo; 293 DA). A significantly greater proportion of patients in all regions who received roxadustat had a Hb response without rescue therapy vs placebo (Europe: 77.9% vs 16.5%, difference of proportion [DOP] 61.4%, 95% CI: 56.5-66.2; US: 75.4% vs 8.3%, DOP 67.2%, 95% CI: 62.7-71.6; and other: 83.4% vs 5.5%, DOP 78.0%, 95% CI: 75.4-80.5) and a numerically greater proportion in both regions vs DA (Western Europe/Israel: 93.9% vs 83.5%, DOP 10.4%, 95% CI: 1.2-19.6; Central/Eastern Europe: 86.5% vs 75.4%, DOP 10.9%, 95% CI: 3.6-18.3). Mean Hb CFB was significantly greater with roxadustat vs placebo in Europe (2.01 vs 0.37 g/dL, LSMD 1.70, 95% CI: 1.55-1.84), US (1.80 vs 0.21 g/dL, LSMD 1.67, 95% CI: 1.53-1.82), and other (1.80 vs 0.06 g/dL, LSMD 1.77, 95% CI: 1.64-1.89) (all P&lt;0.0001) and similar vs DA in Western Europe/Israel (1.64 vs 1.75 g/dL, LSMD -0.03, 95% CI: -0.30 to 0.23, P=0.80) and Central/Eastern Europe (1.94 vs 1.88 g/dL, LSMD 0.03, 95% CI: -0.14 to 0.21, P=0.72). The range in incidence for select TEAEs (arteriovenous fistula thrombosis, deep vein thrombosis, nausea, and seizure) was: 0.3-8.4% for roxadustat and 0.2-4.3% for placebo in Europe; 0.8-10.8% for roxadustat and 0.1-7.0% for placebo in non-Europe; 0-12.1% for roxadustat and 0-11.8% for DA in Western Europe/Israel; 0.4-6.3% for roxadustat and 0-3.4% for DA in Central/Eastern Europe. Conclusion In patients with anaemia and stage 3-5 NDD CKD, roxadustat was more effective than placebo for correcting Hb and generating Hb response without rescue therapy in Europe, the US, and other countries. It was similarly effective as DA for correcting Hb and generating a Hb response without rescue therapy in Western Europe/Israel and Central/Eastern Europe. The incidence of select TEAEs was comparable and relatively low in all regions.

scholarly journals Hypoxia-inducible factor prolyl hydroxylase domain inhibitor may maintain hemoglobin synthesis at lower serum ferritin and transferrin saturation levels than darbepoetin alfa

PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252439
Author(s):  
Chie Ogawa ◽  
Ken Tsuchiya ◽  
Naohisa Tomosugi ◽  
Kunimi Maeda
Keyword(s):  
Iron Deficiency ◽  
Serum Ferritin ◽  
Darbepoetin Alfa ◽  
Reference Group ◽  
Hypoxia Inducible Factor ◽  
Transferrin Saturation ◽  
Prolyl Hydroxylase ◽  
Logistic Analysis ◽  
Cutoff Values ◽  
Prolyl Hydroxylase Domain

Background Hypoxia-inducible factor (HIF) prolyl hydroxylase domain inhibitors, which have recently become clinically available for treating renal anemia, are attracting attention for their novel mechanisms of action. Methods Relationships of reticulocyte hemoglobin content (CHr), which reflects recent Hb synthesis, with serum ferritin (s-ft) and transferrin saturation (TSAT) were examined in 30 patients on hemodialysis after switching from darbepoetin alfa (DA) to roxadustat (Rox). Iron deficiency was defined as CHr < 32.0 pg. Cutoff values of s-ft and TSAT were determined using receiver operating characteristic curves for the endpoint CHr ≥ 32.0 pg. Logistic analysis was performed with the reference group having s-ft or TSAT below the corresponding cutoff value (low vs high). Results With the endpoint CHr ≥ 32.0 pg on Day 0, cutoff values for s-ft and TSAT were respectively 49.7 ng/mL and 21.6% on Day 0 and 35.5 ng/mL and 16.2% on Day 28. With the endpoint CHr ≥ 32.0 pg on Day 28, cutoff values for s-ft and TSAT on Day 0 were 81.6 ng/mL and 23.9%, respectively. According to multivariable logistic analysis, the odds ratios of CHr ≥ 32.0 pg on Day 0 were significantly higher for high TSAT on Day 0 [34.7 (95% CI 2.42–131.0), p<0.003] and Day 28 [24.8 (95% CI 2.75–224.0), p = 0.004]. There were no significant differences by s-ft. Odd ratios of CHr ≥ 32.0 pg on Day 28 were also significantly higher for high s-ft on Day 0 [16.0 (95% CI 1.57–163.0), p = 0.019] and high TSAT on Day 0 [13.5 (95% CI 1.24–147.0), p<0.033]. Conclusions Our results suggest Hb synthesis was maintained with lower TSAT and s-ft during Rox therapy compared with DA therapy. To avoid iron deficiency during the 4 weeks after switching DA to Rox, ideal s-ft and TSAT levels before the switch are 81.6 ng/mL and 23.9%, respectively.

scholarly journals CORRECTING OF ANEMIA USING IRON SUCROSE IN PATIENTS WITH CHRONIC KIDNEYDISEASE STAGE VD ON HEMODIALYSIS

2014 ◽  
pp. 13-21
Author(s):  
I. Dudar ◽  
I. Shifris ◽  
Y. Gonchar ◽  
V. Savchuk ◽  
O. Loboda ◽  
...  
Keyword(s):  
Iron Deficiency ◽  
Serum Ferritin ◽  
Transferrin Saturation ◽  
Intravenous Iron ◽  
Iron Sucrose ◽  
Efficacy And Safety ◽  
Before And After ◽  
Main Factors ◽  
Exchange Parameters ◽  
Iron Exchange

Anemia is a common complication of CKD. Iron deficiency is one of a leading cause of anemia in HD patients. The causes of iron deficiency in these patients are multifactorial. Main factors that contribute to iron deficiency in HD patients are reduction intake and impaired intestinal absorption of dietary iron, blood losses, chronic inflammation and increased iron requirements during therapy with erythropoiesis–stimulating agents. Aim.The aim was to study efficacy and safety of iron sucrose (Venofer) in HD patients with anemia. Materials and methods. This study was an retrospective, epidemiologic, performed from 2010 to 2014 years. The study included 69 HD patients with anemia from dialysis single–center. 38 (55.1%) patients were men, average age 49,53 ± 3,9years and the most common cause of ESRD was glomerulonephritis (37 patients, 53.6%). Hemoglobin value was analyzed weekly. The levels of serum ferritin and transferrin saturation, were determined before and after treatment with Venofer. Results. Treatment with the Venofer resulted a significant increase of hematological and iron exchange parameters. At 2 – 3 weeks of therapy, hemoglobin levels increased by 7,6% and 10,7%, respectively. 14 days after the last dose Venoer serum ferritin and transferrin saturation levels have increased by 58% and 55%, respectively. Conclusions. Intravenous iron is the preferred route of administration in HD patients. Venofer showing a significant increase both of hemoglobin and iron exchange markers levels on a background of insignificant frequency of treatment–related adverse events.

Treatment of varicose tributaries with sclerotherapy with polidocanol 0.5 % foam

VASA ◽  
2010 ◽  
Vol 39 (2) ◽  
pp. 169-174 ◽  
Author(s):  
Reich-Schupke ◽  
Weyer ◽  
Altmeyer ◽  
Stücker
Keyword(s):  
Scientific Evidence ◽  
Daily Practice ◽  
Severe Adverse Effect ◽  
Safe Procedure ◽  
Efficacy And Safety ◽  
Foam Sclerotherapy ◽  
History Of ◽  
One Year ◽  
Additional Therapy

Background: Although foam sclerotherapy of varicose tributaries is common in daily practice, scientific evidence for the optimal sclerosant-concentration and session-frequency is still low. This study aimed to increase the knowledge on foam sclerotherapy of varicose tributaries and to evaluate the efficacy and safety of foam sclerotherapy with 0.5 % polidocanol in tributaries with 3-6 mm in diameter. Patients and methods: Analysis of 110 legs in 76 patients. Injections were given every second or third day. A maximum of 1 injection / leg and a volume of 2ml / injection were administered per session. Controls were performed approximately 6 months and 12 months after the start of therapy. Results: 110 legs (CEAP C2-C4) were followed up for a period of 14.2 ± 4.2 months. Reflux was eliminated after 3.4 ± 2.7 injections per leg. Insufficient tributaries were detected in 23.2 % after 6.2 ± 0.9 months and in 48.2 % after 14.2 ± 4.2 months, respectively. Only 30.9 % (34 / 110) of the legs required additional therapy. In 6.4 % vein surgery was performed, in 24.5 % similar sclerotherapy was repeated. Significantly fewer sclerotherapy-sessions were required compared to the initial treatment (mean: 2.3 ± 1.4, p = 0.0054). During the whole study period thrombophlebitis (8.2 %), hyperpigmentation (14.5 %), induration in the treated region (9.1 %), pain in the treated leg (7.3 %) and migraine (0.9 %) occurred. One patient with a history of thrombosis developed thrombosis of a muscle vein (0.9 %). After one year there were just hyperpigmentation (8.2 %) and induration (1.8 %) left. No severe adverse effect occurred. Conclusions: Foam sclerotherapy with injections of 0.5 % polidocanol every 2nd or 3rd day, is a safe procedure for varicose tributaries. The evaluation of efficacy is difficult, as it can hardly be said whether the detected tributaries in the controls are recurrent veins or have recently developed in the follow-up period. The low number of retreated legs indicates a high efficacy and satisfaction of the patients.

Ponatinib: A Review of Efficacy and Safety

2018 ◽  
Vol 18 (9) ◽  
pp. 847-856 ◽  
Author(s):  
Fulvio Massaro ◽  
Matteo Molica ◽  
Massimo Breccia
Keyword(s):  
Kinase Inhibitor ◽  
Tolerability Profile ◽  
Third Generation ◽  
Efficacy And Safety ◽  
Future Perspectives ◽  
General Management ◽  
T315i Mutation ◽  
Baseline Characteristics ◽  
Management Recommendations ◽  
Cardiovascular Profile

Ponatinib is a third generation kinase inhibitor designed to overcome the gatekeeper T315I mutation. In different trials this drug showed inhibitory activity against native BCR-ABL1 kinase and several ABL1 mutations. For this reason, ponatinib is currently indicated for the treatment of chronic myeloid leukaemia (CML) in every phase of disease resistant and/or intolerant to dasatinib and nilotinib and for whom imatinib is not indicated anymore or for patients with T315I mutation. The drug is also indicated for Ph+ acute lymphoblastic leukaemia (ALL). Ponatinib was temporarily suspended in 2013 for the occurrence of cardiovascular thrombotic events. Since then, different investigators analyzed baseline characteristics of patient candidates for ponatinib, especially cardiovascular profile, in order to describe general management recommendations in this setting. In this review, clinical trials data about the use of ponatinib in CML and Ph+ ALL patients will be discussed. It will be focused also about the safety and tolerability profile of the drug and future perspectives of employment.

Roxadustat for anemia in patients with end-stage renal disease incident to dialysis

2021 ◽  
Author(s):  
Robert Provenzano ◽  
Evgeny Shutov ◽  
Liubov Eremeeva ◽  
Svitlana Korneyeva ◽  
Lona Poole ◽  
...  
Keyword(s):  
Rescue Therapy ◽  
Controlled Trial ◽  
Epoetin Alfa ◽  
Open Label ◽  
Treatment Groups ◽  
Intention To Treat ◽  
Primary Endpoints ◽  
Stage Renal Disease ◽  
End Stage ◽  
Event Rates

Abstract Background We evaluated the efficacy and safety of roxadustat vs. epoetin alfa for the treatment of chronic kidney disease (CKD) related anemia in patients new to dialysis. Methods This was a phase 3, open-label, epoetin alfa-controlled trial. Eligible adults were on hemodialysis/peritoneal dialysis for ≥2 weeks and ≤4 months before randomization and had mean hemoglobin ≤10.0 g/dL. Primary endpoints were mean hemoglobin (g/dL) change from baseline averaged over weeks 28–52 regardless of rescue therapy (non-inferiority criterion: lower limit of 95% CI for treatment difference &gt; −0.75) and percentage of patients achieving a hemoglobin response between weeks 1–24 censored for rescue therapy (non-inferiority margin for between-group difference: −15%). Adverse events were monitored. Results The intention-to-treat population included patients randomized to roxadustat (n = 522) or epoetin alfa (n = 521). Mean (SD) hemoglobin changes from baseline averaged over weeks 28–52 were 2.57 (1.27) and 2.36 (1.21) in the roxadustat and epoetin alfa groups. Roxadustat was non-inferior (least-squares mean difference: 0.18 [95% CI: 0.08, 0.29]) to epoetin alfa. Percentages of patients with a hemoglobin response were 88.2% and 84.4% in the roxadustat and epoetin alfa groups. Roxadustat was non-inferior to epoetin alfa (treatment-group difference: 3.5% [95% CI: −0.7%, 7.7%]). Adverse event rates were comparable between treatment groups. Conclusions Roxadustat was efficacious for correcting and maintaining hemoglobin levels compared to epoetin alfa. Roxadustat had an acceptable safety profile.

scholarly journals Prospective, Open-label Trial to Evaluate Efficacy of Lyophilized Fecal Microbiota Transplantation for Treatment of Recurrent C. difficile Infection

2017 ◽  
Vol 4 (suppl_1) ◽  
pp. S383-S384
Author(s):  
Peyman Goldeh ◽  
Peter Kim ◽  
Salaheddin Abouanaser ◽  
Eric Partlow ◽  
Patricia Beckett ◽  
...  
Keyword(s):  
Fecal Microbiota Transplantation ◽  
Controlled Trial ◽  
Similar Efficacy ◽  
Fecal Microbiota ◽  
Efficacy And Safety ◽  
Open Label ◽  
Retention Enema ◽  
Recurrent Clostridium Difficile Infection ◽  
Laboratory Facility ◽  
History Of

Abstract Background Fecal microbiota transplantation (FMT) has shown to be effective for recurrent Clostridium difficile infection (rCDI). However, significant laboratory costs for donor screening and a lack of suitable donors and laboratory facility have restricted the availability of the treatment. In order to expand access to FMT, we have investigated the efficacy of lyophilized FMT, comparing it to the published historical efficacy of frozen FMT in preventing further episodes of CDI in patients with a history of rCDI. This study was designed to be open-labeled to expedite and minimize costs associated with conducting a two-armed randomized controlled trial, given that the efficacy of frozen FMT is known to be 85%. Additionally, using lyophilized FMT offers two major advantages: 1) its prolonged shelf life reduces cost because fewer donors need to be screened; and 2) it can be transported without freezing. Methods This is an open-labeled, prospective study involving 50 patients with a history of 2 or more rCDI who have failed at least 1 course of tapered vancomycin therapy. Eligible patients received 2 lyophilized FMT via retention enema within 8 days of each treatment and were followed for 13 weeks post last FMT to determine efficacy and safety of FMT. Results The efficacy of lyophilized FMTs in preventing further episodes of CDI in patients with rCDI was 80%. The adverse events associated with lyophilized FMT were similar to frozen FMT. Conclusion Lyophilized FMT in treating rCDI showed similar efficacy and safety to frozen FMT. Lyophilized FMT appears to be promising in preventing further episode of CDI and increasing accessibility for patients with rCDI. Disclosures All authors: No reported disclosures.

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