Managing multicenter clinical trials (MCTs) is demanding and complex. The Randomized controlled Evaluation of high-volume hemofiltration in adult burn patients with Septic shoCk and acUte kidnEy injury (RESCUE) trial was a prospective, MCT involving the impact of high-volume hemofiltration continuous renal replacement therapy on patients experiencing acute kidney injury and septic shock. Ten clinical burn centers from across the United States were recruited to enroll a target sample size of 120 subjects. This manuscripts reviews some of the obstacles and knowledge gained while coordinating the RESCUE trial. The first subject was enrolled in February 2012, 22 months after initial IRB approval and 29 months from the time the grant was awarded. The RESCUE team consisted of personnel at each site, including the lead site, a data coordination center, data safety monitoring board, steering committees, and the sponsor. Seven clinical sites had enrolled 37 subjects when enrollment stopped in February 2016. Obstacles included changes in institutional review boards, multiple layers of review, staffing changes, creation and amendment of study documents and procedures, and finalization of contracts. Successful completion of a MCT requires a highly functional research team with sufficient patient population, expertise, and research infrastructure. Additionally, realistic timelines must be established with strategies to overcome challenges. Inevitable obstacles should be discussed in the pretrial phase and continuous correspondence must be maintained with all relevant research parties throughout all phases of study.