Cluster-Randomized Trial of Devices to Prevent Catheter-Related Bloodstream Infection.

Central venous catheters (CVCs) contribute disproportionately to bloodstream infection (BSI) and, by extension, to infection-related hospitalization, mortality, and health care costs in patients undergoing dialysis. Recent product advancements may reduce BSIs, but a sufficiently powered comparative-effectiveness study is needed to facilitate evidence-based patient care decisions. In a 13-month, prospective, cluster-randomized, open-label trial, we compared BSI rates in facilities using ClearGuard HD antimicrobial barrier caps (ClearGuard group) with those in facilities using Tego hemodialysis connectors plus Curos disinfecting caps (Tego+Curos group). Forty DaVita dialysis facilities in the United States were pair-matched by BSI rate, number of patients using CVCs, and geographic location, and then cluster randomized 1:1. We enrolled all adult patients undergoing dialysis with CVCs at these facilities, except those allergic to heparin or chlorhexidine. Overall, 1671 patients participated in the study, accruing >183,000 CVC-days. The study outcome was positive blood culture (PBC) rate as an indicator of BSI rate. We calculated results at the cluster level and adjusted for the facility cluster effect. During a 3-month run-in period immediately before study interventions, the groups had similar BSI rates (P=0.8). During the 13-month intervention period that immediately followed, the ClearGuard group had a BSI rate significantly lower than that of the Tego+Curos group (0.28 versus 0.75 PBCs per 1000 CVC-days, respectively; P=0.001). No device-related adverse events were reported. In conclusion, compared with Tego connectors plus Curos caps, ClearGuard HD antimicrobial barrier caps significantly lowered the rate of catheter-related BSIs in patients undergoing hemodialysis using CVCs, representing an important advancement in hemodialysis patient care.

Safety of intravenous ferric carboxymaltose versus oral iron in patients with nondialysis-dependent CKD: an analysis of the 1-year FIND-CKD trial.

BACKGROUND: The evidence base regarding the safety of intravenous (IV) iron therapy in patients with chronic kidney disease (CKD) is incomplete and largely based on small studies of relatively short duration. METHODS: FIND-CKD (ClinicalTrials.gov number NCT00994318) was a 1-year, open-label, multicenter, prospective study of patients with nondialysis-dependent CKD, anemia and iron deficiency randomized (1:1:2) to IV ferric carboxymaltose (FCM), targeting higher (400-600 µg/L) or lower (100-200 µg/L) ferritin, or oral iron. A post hoc analysis of adverse event rates per 100 patient-years was performed to assess the safety of FCM versus oral iron over an extended period. RESULTS: The safety population included 616 patients. The incidence of one or more adverse events was 91.0, 100.0 and 105.0 per 100 patient-years in the high ferritin FCM, low ferritin FCM and oral iron groups, respectively. The incidence of adverse events with a suspected relation to study drug was 15.9, 17.8 and 36.7 per 100 patient-years in the three groups; for serious adverse events, the incidence was 28.2, 27.9 and 24.3 per 100 patient-years. The incidence of cardiac disorders and infections was similar between groups. At least one ferritin level ≥800 µg/L occurred in 26.6% of high ferritin FCM patients, with no associated increase in adverse events. No patient with ferritin ≥800 µg/L discontinued the study drug due to adverse events. Estimated glomerular filtration rate remained the stable in all groups. CONCLUSIONS: These results further support the conclusion that correction of iron deficiency anemia with IV FCM is safe in patients with nondialysis-dependent CKD.

Knowing what we do and doing what we should: quality assurance in hemodialysis.

An international group of around 50 nephrologists and scientists, including representatives from large dialysis provider organisations, formulated recommendations on how to develop and implement quality assurance measures to improve individual hemodialysis patient care, population health and cost effectiveness. Discussed were methods thought to be of highest priority, those clinical indicators which might be most related to meaningful patient outcomes, tools to control treatment delivery and the role of facilitating computerized expert systems. Emphasis was given to the use of new technologies such as measurement of online dialysance and ways of assessing fluid status. The current evidence linking achievement of quality criteria with patient outcomes was reviewed. This paper summarizes useful processes and quality measures supporting quality assurance that have been agreed across the expert panel. It also notes areas where more understanding is required.

Urgent-start peritoneal dialysis: Association with outcomes.

The majority of end-stage kidney disease (ESKD) patients start dialysis without adequate pre-dialysis planning. Of these patients, the vast majority initiate in-centre haemodialysis using a central venous catheter (ICHD-CVC). A minority utilise urgent-start peritoneal dialysis (USPD), whereby a peritoneal dialysis catheter is placed and used for dialysis without the usual 2-4-week waiting period. In this multicentre, retrospective study of adult patients initiating dialysis during 2018, we compared outcomes among patients utilising these two dialysis initiation routes. Patients who initiated dialysis via ICHD-CVC were matched 1:1 to patients who utilised USPD on the basis of aetiology of ESKD, race, diabetes status and insurance type. Hospitalisation and mortality were evaluated from dialysis initiation through the first of death, transplant, loss to follow-up or study end (30 June 2019). Outcomes were compared using models adjusted for age and sex. A total of 717 USPD patients were matched to ICHD-CVC patients. During follow-up, USPD patients were hospitalised at a rate of 1.21 admissions/patient-year (pt-yr) versus 1.51 admissions/pt-yr for ICHD-CVC. This corresponded to a 24% lower rate of hospitalisation among USPD patients (adjusted incidence rate ratio 0.76, 95% confidence interval [CI] 0.65-0.88). Mortality rates were 0.08 and 0.11 deaths/pt-yr among USPD patients and ICHD-CVC patients, respectively (adjusted hazard ratio 0.84, 95% CI 0.62, 1.15). These findings suggest that more widespread adoption of USPD may be beneficial among patients with limited pre-dialysis planning.

Analytical and biological variation in measures of anemia and iron status in patients treated with maintenance hemodialysis.

BACKGROUND: To make informed decisions in dosing erythropoiesis-stimulating agents and intravenous iron therapy, clinicians must determine whether differences between current and previous test results for anemia and iron status markers reflect expected variation, a significant change, or an actual trend. STUDY DESIGN: Prospective observational cohort study. SETTING & PARTICIPANTS: 30 patients undergoing thrice-weekly in-center hemodialysis. PREDICTOR: Within-patient biological variations in hemoglobin (Hb) level, hematocrit (Hct), reticulocyte Hb content, transferrin saturation (TSAT), and ferritin level were determined over 12 consecutive treatment days. OUTCOMES & MEASUREMENTS: We separately measured same-sample analytical variation and within-patient biological variation (coefficient of variation), then calculated the number of sampling days needed to determine the true or homeostatic value for each analyte with 95% probability. We also evaluated whether results differed among the first, second, and third dialysis days of the week. RESULTS: Biological variation differed by analyte. Hb level (4.0%), Hct (4.0%), and reticulocyte Hb content (4.8%) showed much lower variation than TSAT (38.2%) or ferritin level (15.1%). Analytical variation ranged from 2.0%-6.9% for all analytes. We found that one sample day would be sufficient to establish the true mean Hb level or Hct within a level of closeness+/-20% and 95% probability. For the same levels of closeness and probability, one sample day would be needed for reticulocyte Hb content, 15 for TSAT, and 3 for ferritin level. No pairwise comparison for any of the 5 analytes yielded a significant difference between results obtained on the first, second, or third dialysis day of the week. LIMITATIONS: These findings may not apply to other patient populations. CONCLUSIONS: Low biological variation renders Hb level, Hct, and reticulocyte Hb content, but not TSAT and ferritin level, suitable for trend analysis using results from 2 successive samples. TSAT and ferritin test results, unlike reticulocyte Hb content, have limited value in evaluating changes in iron status within individual hemodialysis patients.

Impact of Rescheduling a Missed Hemodialysis Treatment on Clinical Outcomes.

RATIONALE & OBJECTIVE: Among patients treated with in-center hemodialysis (HD), missed treatments are associated with higher subsequent rates of hospitalization and other adverse outcomes compared with attending treatment. The objective of this study was to determine whether and to what degree attending a rescheduled treatment on the day following a missed treatment ameliorates these risks. STUDY DESIGN: Retrospective, observational. SETTING & PARTICIPANTS: Included patients were those who were, as of any of 12 index dates during 2014, adult Medicare beneficiaries treated with in-center HD (vintage ≥ 90 days) on a Monday/Wednesday/Friday schedule. EXPOSURE: Treatment attendance on the index date and the subsequent day. OUTCOMES: Hospital admissions, emergency department visits, mortality, blood pressure, and anemia measures, considered during the 7- and 30-day periods following exposure. ANALYTICAL APPROACH: In parallel analyses, patients who missed or rescheduled treatment were each matched (1:5) to patients who attended treatment on the index date on the basis of index day of week and propensity score. Within the matched cohorts, outcomes were compared across exposures using repeated-measures generalized linear models. RESULTS: Compared with attending treatment (N = 19,260), a missed treatment (N = 3,852) was associated with a 2.09-fold higher rate of hospitalization in the subsequent 7 days; a rescheduled treatment (N = 2,128) was associated with a 1.68-fold higher rate of hospitalization than attending (N = 10,640). Compared with attending treatment, hospitalization rates were 1.39- and 1.28-fold higher among patients who missed and rescheduled treatment, respectively, during the 30-day outcome period. Emergency department visits followed a similar pattern of associations as hospitalization. No statistically significant associations were observed with respect to mortality for either missed or rescheduled treatments compared with attending treatment. LIMITATIONS: Possible influence of unmeasured confounding; unknown generalizability to patients with non-Medicare insurance. CONCLUSIONS: Attending a rescheduled in-center HD treatment attenuates but does not fully mitigate the adverse effects of a missed treatment.

Large-dose intravenous ferric carboxymaltose injection for iron deficiency anemia in heavy uterine bleeding: a randomized, controlled trial.

BACKGROUND: The objective was to evaluate efficacy and safety of rapid, large-dose intravenous (IV) administration of ferric carboxymaltose compared to oral iron in correcting iron deficiency anemia due to heavy uterine bleeding. STUDY DESIGN AND METHODS: In a randomized, controlled trial, 477 women with anemia, iron deficiency, and heavy uterine bleeding were assigned to receive either IV ferric carboxymaltose (or= 12 g/dL) of anemia (73% vs. 50%, p < 0.001). Patients treated with ferric carboxymaltose compared to those prescribed ferrous sulfate reported greater gains in vitality and physical function and experienced greater improvement in symptoms of fatigue (p < 0.05). There were no serious adverse drug events. CONCLUSIONS: In patients with iron deficiency anemia due to heavy uterine bleeding, rapid IV administration of large doses of a new iron agent, ferric carboxymaltose, is more effective than oral iron therapy in correcting anemia, replenishing iron stores, and improving quality of life.

Intravenous ferric carboxymaltose compared with oral iron in the treatment of postpartum anemia: a randomized controlled trial.

OBJECTIVE: To estimate efficacy of rapid, large-dose intravenous (IV) administration of ferric carboxymaltose compared with oral iron therapy in anemic postpartum women. METHODS: In a randomized, controlled trial, we assigned anemic women (hemoglobin [Hb] less than or equal to 10 g/dL) within 10 days postpartum to receive either IV ferric carboxymaltose (less than or equal to 1,000 mg over 15 minutes, repeated weekly to achieve a total calculated replacement dose) or ferrous sulfate (FeSO(4)) 325 mg orally thrice daily for 6 weeks. RESULTS: One hundred seventy-four patients received 350 IV doses of ferric carboxymaltose (mean total dose 1,403.1 mg) in 3, 2, or 1 injection (10.9%, 79.3%, or 9.8% of patients, respectively); 178 received FeSO(4). Patients assigned to IV ferric carboxymaltose compared with those assigned to oral iron achieved a Hb rise greater than or equal to 2.0 g/dL earlier (7.0 compared with 14.0 days, P<.001), were more likely to achieve a Hb rise greater than or equal to 3.0 g/dL at any time (86.3% compared with 60.4%, P<.001), and were more likely to achieve a Hb greater than 12.0 g/dL (90.5% compared with 68.6%, P<.001). A similar proportion of patients achieved a Hb rise greater than or equal to 2.0 g/dL (96.4% compared with 94.1%, IV compared with oral, P=.443). There were no serious adverse drug reactions. CONCLUSION: Large-dose IV ferric carboxymaltose administration is a new iron agent that is effective for the treatment of postpartum anemia. When compared with oral ferrous sulfate, IV ferric carboxymaltose is better tolerated, prompts a more rapid Hb response, and corrects anemia more reliably. CLINICAL TRIAL REGISTRATION: ClinicalTrials.gov, www.clinicaltrials.gov, NCT00396292 LEVEL OF EVIDENCE: I.

Hepcidin Response to Iron Therapy in Patients with Non-Dialysis Dependent CKD: An Analysis of the FIND-CKD Trial.

Hepcidin is the key regulator of iron homeostasis but data are limited regarding its temporal response to iron therapy, and response to intravenous versus oral iron. In the 56-week, open-label, multicenter, prospective, randomized FIND-CKD study, 626 anemic patients with non-dialysis dependent chronic kidney disease (ND-CKD) and iron deficiency not receiving an erythropoiesis stimulating agent were randomized (1:1:2) to intravenous ferric carboxymaltose (FCM), targeting higher (400-600µg/L) or lower (100-200µg/L) ferritin, or to oral iron. Serum hepcidin levels were measured centrally in a subset of 61 patients. Mean (SD) baseline hepcidin level was 4.0(3.5), 7.3(6.4) and 6.5(5.6) ng/mL in the high ferritin FCM (n = 17), low ferritin FCM (n = 16) and oral iron group (n = 28). The mean (SD) endpoint value (i.e. the last post-baseline value) was 26.0(9.1),15.7(7.7) and 16.3(11.0) ng/mL, respectively. The increase in hepcidin from baseline was significantly smaller with low ferritin FCM or oral iron vs high ferritin FCM at all time points up to week 52. Significant correlations were found between absolute hepcidin and ferritin values (r = 0.65, p<0.001) and between final post-baseline increases in both parameters (r = 0.70, p<0.001). The increase in hepcidin levels over the 12-month study generally mirrored the cumulative iron dose in each group. Hepcidin and transferrin saturation (TSAT) absolute values showed no correlation, although there was an association between final post-baseline increases (r = 0.42, p<0.001). Absolute values (r = 0.36, p = 0.004) and final post-baseline increases of hepcidin and hemoglobin (p = 0.30, p = 0.030) correlated weakly. Baseline hepcidin levels were not predictive of a hematopoietic response to iron therapy. In conclusion, hepcidin levels rose in response to either intravenous or oral iron therapy, but the speed and extent of the rise was greatest with intravenous iron targeting a higher ferritin level. However neither the baseline level nor the change in hepcidin was able to predict response to therapy in this cohort.

Effect of intravenous iron sucrose in peritoneal dialysis patients who receive erythropoiesis-stimulating agents for anemia: a randomized, controlled trial.

Although iron therapy is essential to optimize use of erythropoiesis-stimulating agents (ESA), randomized, controlled trials have heretofore been unavailable to evaluate reliably the efficacy of intravenous iron as an adjuvant to ESA treatment in peritoneal dialysis (PD) patients. In a multicenter trial, patients who had anemia, PD-dependent chronic kidney disease, stable ESA therapy, and a broad range of iron status (ferritin < or = 500 ng/ml, transferrin saturation < or = 25%) were randomly assigned to receive either 1 g of iron sucrose intravenously in three divided doses (300 mg over 1.5 h on days 1 and 15, 400 mg over 2.5 h on day 29) or no supplemental iron. No serious adverse drug events occurred after intravenous iron administration. The primary end point, peak hemoglobin increase, was higher (1.3 +/- 1.1 versus 0.7 +/- 1.1, mean +/- SD; P = 0.0028), and anemia intervention (transfusion, increase in ESA dose, or intravenous iron therapy not called for in protocol) occurred later (P = 0.0137) and less often in intravenous iron-treated patients compared with untreated control subjects (one of 66 [1.3%] versus five of 30 [16.7%]). Among patients who did not require intervention, iron-treated patients showed a calculated net ESA dose decrease compared with untreated control subjects. Baseline iron status did not predict responsiveness to intravenous iron therapy. Intravenous iron sucrose is an effective adjunct to ESA therapy in anemic patients with PD-dependent chronic kidney disease and is administered safely as 300 mg over 1.5 h or 400 mg over 2.5 h. Evidence of iron deficiency at baseline is not required to demonstrate intravenous iron efficacy.

Benchmarking iron dextran sensitivity: reactions requiring resuscitative medication in incident and prevalent patients.

BACKGROUND: Reliable information on the incidence of severe reactions to iron dextran is limited. Administration of agents of resuscitation in acute anaphylaxis may serve as a marker to quantify life-threatening adverse drug reactions. METHODS: To determine the incidence of the most serious reactions to intravenous (i.v.) iron dextran, we searched the Gambro Healthcare US medical database for evidence of same-day administration of both i.v. iron dextran and parenteral adrenaline, corticosteroids or antihistamines. We confirmed each case as an iron dextran sensitivity reaction by direct inquiry. We also determined the total reported number of suspected adverse iron dextran reactions. RESULTS: During the 16 month study period, we determined that 1,066,099 doses of i.v. iron dextran were given to 48,509 patients, including 20,213 patients who had not previously received iron dextran (iron dextran naïve). We identified seven patients who experienced reactions requiring resuscitative agents, all in response to a test dose (five patients) or first therapeutic dose (two patients), and therefore all in the iron-naïve (incident) group. Thus, we found the incidence of iron dextran reactions requiring resuscitative agents to be 0.035% (7 out of 20,213). No reaction was fatal. In a combined group of incident and prevalent patients, we found 337 total reports of suspected adverse reactions to iron dextran, without regard to severity of reaction, yielding an overall per patient adverse drug event (ADE) rate of 0.69% (337 out of 48,509) and per exposure rate of 0.03% (337 out of 1,066,099). CONCLUSIONS: The incidence of reactions to iron dextran requiring resuscitative medications, per exposure or per patient, is approximately 0.035%. Reactions of this severity occur after either the test dose or first dose of iron dextran.

A randomized, controlled trial comparing IV iron sucrose to oral iron in anemic patients with nondialysis-dependent CKD.

BACKGROUND: Although iron deficiency frequently complicates anemia in patients with nondialysis-dependent CKD (ND-CKD), the comparative treatment value of IV iron infusion and oral iron supplementation has not been established. METHODS: In a randomized, controlled multicenter trial, we compared the efficacy of iron sucrose, given as 1 g in divided IV doses over 14 days, with that of ferrous sulfate, given 325 mg orally thrice daily for 56 days in patients with ND-CKD stages 3 to 5, Hb < or =11 g/dL, TSAT < or =25%, and ferritin < or =300 ng/mL. Epoetin/darbepoetin therapy, if any, was not changed for eight weeks prior to or during the study. RESULTS: The proportion of patients achieving the primary outcome (Hb increase > or =1 g/dL) was greater in the IV iron treatment group than in the oral iron treatment group (44.3% vs. 28.0%, P= 0.0344), as was the mean increase in Hb by day 42 (0.7 vs. 0.4 g/dL, P= 0.0298). Compared to those in the IV iron group, patients in the oral iron treatment group showed a greater decline in GFR during the study (-4.40 vs. -1.45 mL/min/1.73m2, P= 0.0100). No serious adverse drug events (ADE) were seen in patients administered IV iron sucrose as 200 mg IV over two to five minutes, but drug-related hypotension, including one event considered serious, occurred in two females weighing less than 65 kg after 500 mg doses were given over four hours. CONCLUSION: IV iron administration using 1000 mg iron sucrose in divided doses is superior to oral iron therapy in the management of ND-CKD patients with anemia and low iron indices.