How to set up a clinical trial.

Clinical trials are considered the gold-standard method for the evaluation of healthcare interventions. However, randomised control trials are complex to perform and many researchers, especially those in the early stages of their career, can find it challenging to know where to start set up, contribute to or lead a trial. This guide provides an introduction to trials and also practical advice to help potential investigators complete their clinical trial to time and to budget by signposting the pathway through the complex regulatory landscape. The authors draw on their own recent experiences of running clinical trials and provide tips and tricks for troubleshooting common problems encountered including trial design and documentation.

Hemin Preconditioning Upregulates Heme Oxygenase-1 in Deceased Donor Renal Transplant Recipients: A Randomized, Controlled, Phase IIB Trial.

BACKGROUND: The enzyme heme oxygenase-1 (HO-1) degrades heme and protects against ischemia-reperfusion injury. Monocytes/macrophages are the major source of HO-1 and higher levels improve renal transplant outcomes. Heme arginate (HA) safely induces HO-1 in humans. METHODS: The Heme Oxygenase-1 in renal Transplantation study was a randomized, placebo-controlled, IIb trial to evaluate HA effect on HO-1 upregulation after deceased donor kidney transplantation. 40 recipients were randomized to either 3 mg kg HA or placebo (0.9% NaCl), given preoperatively (day 0) and again on day 2. Recipient blood and urine were collected daily. Graft biopsies were taken preoperatively and on day 5. Primary outcome was HO-1 upregulation in peripheral blood mononuclear cells (PBMCs). Secondary outcomes were graft HO-1 upregulation and injury, urinary biomarkers, and renal function. RESULTS: The HA upregulated PBMC HO-1 protein more than placebo at 24 hours: HA 11.1 ng/mL versus placebo 0.14 ng/mL (P = < 0.0001). The PBMC HO-1 messenger RNA also increased: HA 2.73-fold versus placebo 1.41-fold (P = 0.02). Heme arginate increased day 5 tissue HO-1 protein immunopositivity compared with placebo: HA 0.21 versus placebo -0.03 (P = 0.02) and % HO-1-positive renal macrophage also increased: HA 50.8 cells per high power field versus placebo 22.3 (P = 0.012). Urinary biomarkers were reduced after HA but not significantly. Histological injury and renal function were similar but the study was not powered for this. Adverse events were equivalent between groups. CONCLUSIONS: The primary outcome was achieved and demonstrated for the first time that HA safely induces HO-1 in transplant recipients. Planned larger studies will determine the impact of HO-1 upregulation on clinical outcomes and evaluate the benefit to patients at risk of ischemia-reperfusion injury.

Jejunal diverticulum with ectopic pancreatic mucosa: was it really a Meckel's diverticulum?

We report the case of a 72-year-old man who underwent surgery for a jejunal intussusception caused by an infarcted mass on the antimesenteric surface of the small bowel approximately 90 cm from the duodenojejunal flexure. The specimen was reported as an infarcted diverticulum containing heterotopic pancreatic mucosa in keeping with infarcted Meckel's diverticulum. We initially wished to establish when the term "Meckel's diverticulum" should be used. The anatomical site in the present case argues against this being a Meckel's diverticulum, a remnant from the mid-gut loop. Non-Meckelian diverticula are usually acquired and often multiple and generally occur on the mesenteric border of the bowel. It is rare for them to contain ectopic mucosa. The diverticulum in our patient thus has features which suggest it may have been congenital. We believe our patient had a rare occurrence of a congenital, but non-Meckelian, diverticulum with associated ectopic epithelium.