J. Sturtevant

The effect of oral iron admiinistration on mycophenolate mofetil absorption in renal transplant recipients: a randomized, controlled trial.

Background. Oral iron supplements are frequently prescribed to renal transplant recipients in the early posttransplant period. A recent trial in seven healthy volunteers demonstrated a significant 91% reduction in mycophenolate mofetil (MMF) absorption when coadministered with oral iron. However, the effect of iron on MMF absorption in renal transplant patients has not been studied. Methods. An open-label, randomized, controlled trial was undertaken in which new renal transplant recipients were randomly allocated to receive iron supplements with a morning dose of MMF, iron supplements given 4 hr after MMF at midday, or no iron supplements. Blood samples were taken for estimation of mycophenolic acid (MPA) area under the curve (AUC) at day 5 posttransplant. The primary endpoint was the day 5 MPA AUC, with secondary endpoints including acute rejection and MMF toxicity in the first 4 weeks posttransplant. Prospective power calculations indicated that a minimum of 13 patients in each group would be required to have a 90% probability of detecting a clinically significant reduction (10 mg/hr/L) in MPA AUC for iron-treated patients. Results. Forty patients completed the study. There were no differences in baseline demographic data between the groups. The mean±standard deviation MPA AUC measurements for the groups receiving no iron (n=13), iron and MMF together (n=14), and iron and MMF spaced apart (n=13) were 34.5±8.7, 33.7±11.4, and 32.1±8.1 &mgr;g/hr/mL, respectively (P =0.82). Rates of acute rejection, cytopenia, infection, and gastrointestinal intolerance were comparable between the groups. Conclusions. There is no significant effect of oral iron supplements on MMF absorption as determined by measured blood concentrations. The practice of routinely giving oral iron in such patients seems safe from an immunosuppression drug-interaction standpoint.

N-of-1 randomized trials to assess the efficacy of gabapentin for chronic neuropathic pain

OBJECTIVE The objective of this study was to compare the efficacy of gabapentin with placebo for neuropathic pain at the individual and population levels. DESIGN This study used an n-of-1 trial methodology with three double-blind, randomized, crossover comparisons of gabapentin with placebo. SETTING This study was carried out at specialist outpatient clinics at two Australian hospitals. Patients. The patients are adults with chronic neuropathic pain. INTERVENTIONS Following a dose-finding period, participants underwent three comparisons of 2-week periods on gabapentin (600-1,800 mg per day) and placebo. The dose-finding period was commenced by 112 patients, of whom 39 had no response so they did not enroll, leaving 73 trial participants. Of these, 48 completed and 7 partially completed their trials, and 18 withdrew. OUTCOME MEASURES The five outcome measures were the visual analog scale (0-10) of pain, sleep interference and functional limitation; frequency of adverse events and medication preference. The aggregate response was determined by weighting the response to each measure equally. RESULTS Of the 55 participants who completed at least one cycle, the aggregate response to gabapentin was better than placebo in 16 (29%), of whom 15 continued gabapentin posttrial. No difference was shown in 38 (69%), and 1 (2%) showed a better response to placebo. Fifteen of these 39 continued gabapentin posttrial. Meta-analysis of the mean scores showed lower mean (standard deviation) scores for gabapentin by 0.8 (0.2) for pain, 0.6 (0.2) for sleep interference, and 0.6 (0.2) for functional limitation. CONCLUSIONS The response rate and mean reduction in symptoms with gabapentin were small. Gabapentin prescribing posttrial was significantly influenced by the trial results.

Off-label use of rituximab in a tertiary Queensland hospital

Background:  Rituximab is a monoclonal antibody directed against CD20, a pan B lymphocyte marker. It is approved in Australia for treatment of CD20‐positive B cell non‐Hodgkin lymphoma and rheumatoid arthritis. There is increasing off‐label use of rituximab in conditions where B cells and autoantibodies play a role in the pathophysiology. Rituximab is not only expensive, but its safety in unregistered indications is uncertain.

Efficacy and side-effect profile of sevelamer hydrochloride used in combination with conventional phosphate binders

Background:  Poor phosphate control is common among patients with end‐stage renal disease. Sevelamer hydrochloride has been demonstrated to be a safe and effective phosphate binder when used as a monotherapy. However, cost limits its usefulness in many countries. Data assessing its effectiveness and safety in combination with conventional phosphate binders are lacking.

Rationale and design of the oral HEMe iron polypeptide Against Treatment with Oral Controlled Release Iron Tablets trial for the correction of anaemia in peritoneal dialysis patients (HEMATOCRIT trial)

BackgroundThe main hypothesis of this study is that oral heme iron polypeptide (HIP; Proferrin® ES) administration will more effectively augment iron stores in erythropoietic stimulatory agent (ESA)-treated peritoneal dialysis (PD) patients than conventional oral iron supplementation (Ferrogradumet®).MethodsInclusion criteria are peritoneal dialysis patients treated with darbepoietin alpha (DPO; Aranesp®, Amgen) for ≥ 1 month. Patients will be randomized 1:1 to receive either slow-release ferrous sulphate (1 tablet twice daily; control) or HIP (1 tablet twice daily) for a period of 6 months. The study will follow an open-label design but outcome assessors will be blinded to study treatment. During the 6-month study period, haemoglobin levels will be measured monthly and iron studies (including transferring saturation [TSAT] measurements) will be performed bi-monthly. The primary outcome measure will be the difference in TSAT levels between the 2 groups at the end of the 6 month study period, adjusted for baseline values using analysis of covariance (ANCOVA). Secondary outcome measures will include serum ferritin concentration, haemoglobin level, DPO dosage, Keys index (DPO dosage divided by haemoglobin concentration), and occurrence of adverse events (especially gastrointestinal adverse events).DiscussionThis investigator-initiated multicentre study has been designed to provide evidence to help nephrologists and their peritoneal dialysis patients determine whether HIP administration more effectively augments iron stores in ESP-treated PD patients than conventional oral iron supplementation.Trial RegistrationAustralia New Zealand Clinical Trials Registry number ACTRN12609000432213.

Heparin-induced thrombocytopenia: recent experience in a large teaching hospital.

Background: Heparin‐induced thrombocytopenia (HIT) is a potentially serious adverse reaction caused by platelet‐activating antibodies.

DABIGATRAN MAY NOT BE AN EFFECTIVE ANTICOAGULANT FOR HAEMODIALYSIS

to impaired autoregulation of glomerular pressure (all had impaired renal function, hypertension treated with angiotensin-converting enzyme inhibitors and/or angiotensin receptor blockers; four were on diuretics for cardiac failure and three had diabetes) making them vulnerable to a reduction in glomerular filtration rate (GFR) following a fall in blood, or renal perfusion, pressure, due to renovascular or cardiac disease or decreased blood volume from what ever cause, including diuretics. As there was no evidence of an obvious cause, for example, symptomatic postural hypotension, active renal disease, intercurrent illness or other causative factor, the presumption is that a combination of their individual susceptibilities to a fall in GFR in association with small, asymptomatic, variations in cardiac function and/or blood pressure were responsible for the multiple, readily reversible, changes in renal function. The net impact of these fluctuations in renal function is unknown. Subjects with chronic renal failure, while often asymptomatic, have a significantly increased cardiac risk and mild neurocognitive impairment (GFR below 45 mL/ min). What is not known is any additional impact of shortterm asymptomatic fluctuations in renal function. On the other hand, the likely precondition for the fluctuations in plasma creatinine, a low glomerular capillary pressure, with a marginal functional reserve, could represent best possible treatment in slowing the rate of progression of renal failure as there is evidence that fall in GFR, of up to 50%, on initiation of antihypertensives predicts better long-term renal prognosis. The best option then in managing such patients, with no evidence of active renal disease, is probably watchful waiting; and being aware that predicting the rate of progression of renal failure is particularly problematic in the presence of large fluctuations in plasma creatinine.

Acute Renal Failure in Patients on Diuretics and/or NSAID, COX-2 inhibitors, ACEI, ARA

To review acute renal failure in patients on one or more target drugs – diuretics, non‐steroidal anti‐inflammatory drugs (NSAID), cyclo‐oxygenase‐2 (COX‐2) inhibitors, angiotensin converting enzyme inhibitors (ACEI) and angiotensin receptor antagonists (ARA).

Audit of Ticarcillan/Clavulanate Usage in a Large Teaching Hospital

To assess compliance with ticarcillin/clavulanate prescribing guidelines, appropriateness of prescribing and to identify any patterns of inappropriate use that may aid in improving prescribing.