Tonsillectomy versus tonsillotomy for recurrent acute tonsillitis in children and adults (TOTO): study protocol for a randomized non-inferiority trial

Background!#!Tonsillectomy is one of the most frequently performed surgeries in children and young adults worldwide. For decades, tonsillectomy was the surgical treatment of choice for recurrent acute tonsillitis. Tonsillotomy was used in some countries as an alternative to tonsillectomy only for the treatment of obstructive sleep apnea in young children. In recent years, an increase of tonsillotomy also to treat recurrent acute tonsillitis can be observed. Therefore, the German Institute for Quality and Efficiency in Health Care (IQWiG) was commissioned by the Federal Joint Committee (G-BA) to investigate whether tonsillotomy offers advantages compared to tonsillectomy. The meta-analysis of the IQWiG including studies until 2016 revealed that the long-term benefits and harms of tonsillotomy compared to tonsillectomy are unclear. Consequently, the G-BA performed a European call for a clinical trial. A consortium of the German Professional Association of ENT-surgeons (BVHNO), the German Society of Oto-Rhino-Laryngology, Head and Neck Surgery (DGHNO-KHC), and the Jena University Hospital were finally selected to perform the TOTO study.!##!Methods!#!TOTO is a multicenter, 1:1 two-arm, randomized non-blinded non-inferiority trial. Four hundred fifty-four patients ≥ 3 years of age will be randomly allocated to undergo either tonsillotomy or tonsillectomy as surgical treatment of recurrent acute tonsillitis. All participants will be followed up for a total of 24 months. The primary outcome is the number of sore throat days experienced over the 24-month follow-up.!##!Discussion!#!TOTO is designed to evaluate the effectiveness and efficiency of tonsillectomy versus tonsillectomy for the management of patients with recurrent acute tonsillitis. Tonsil disease and surgery have a major impact on preschool and school children as well as on economically active young adults, with individual and societal costs through loss of school visits, earnings, and productivity. If tonsillotomy is at least as effective as tonsillectomy but with reduced morbidity, this would reduce costs to the healthcare system and society.!##!Trial registration!#!German Clinical Trials Register DRKS00020823 . Registered on 04 September 2020

Efficacy of team-based collaborative care for distressed patients in secondary prevention of chronic coronary heart disease (TEACH): study protocol of a multicenter randomized controlled trial

Background: Coronary heart disease (CHD) is the leading cause of death and years of life lost worldwide. While effective treatments are available for both acute and chronic disease stages there are unmet needs for effective interventions to support patients in health behaviors required for secondary prevention. Psychosocial distress is a common comorbidity in patients with CHD and associated with substantially reduced health-related quality of life (HRQoL), poor health behavior, and low treatment adherence. Methods: In a confirmatory, randomized, controlled, two-arm parallel group, multicenter behavioral intervention trial we will randomize 440 distressed CHD patients with at least one insufficiently controlled cardiac risk factor to either their physicians' usual care (UC) or UC plus 12-months of blended collaborative care (TeamCare = TC). Trained nurse care managers (NCM) will proactively support patients to identify individual sources of distress and risk behaviors, establish a stepwise treatment plan to improve self-help and healthy behavior, and actively monitor adherence and progress. Additional e-health resources are available to patients and their families. Intervention fidelity is ensured by a treatment manual, an electronic patient registry, and a specialist team regularly supervising NCM via videoconferences and recommending protocol and guideline-compliant treatment adjustments as indicated. Recommendations will be shared with patients and their physicians who remain in charge of patients' care. Since HRQoL is a recommended outcome by both, several guidelines and patient preference we chose a >= 50% improvement over baseline on the HeartQoL questionnaire at 12 months as primary outcome. Our primary hypothesis is that significantly more patients receiving TC will meet the primary outcome criterion compared to the UC group. Secondary hypotheses will evaluate improvements in risk factors, psychosocial variables, health care utilization, and durability of intervention effects over 18-30 months of follow-up. Discussion: TEACH is the first study of a blended collaborative care intervention simultaneously addressing distress and medical CHD risk factors conducted in cardiac patients in a European health care setting. If proven effective, its results can improve long-term chronic care of this vulnerable patient group and may be adapted for patients with other chronic conditions

Planning and design of European prospective randomized trial on the value of drain in parotidectomy

Introduction There are no valid clinical studies on the value of wound drains in parotid surgery. The aim of the current trial is to analyze the influence of the closed wound drain (redon) on the incidence of postoperative complications such as bleeding, wound healing problems, infection, as well as salivary cyst and fistula after superficial or partial parotidectomy. Methods A European-wide multicenter prospective randomized study was planned. The study protocol was prepared by the leading study center (ENT University Hospital Cologne) in cooperation with the ENT University Hospitals Jena and Gottingen. The calculation of the number of cases was carried out with G*Power. The study includes test persons with an indication for parotidectomy for a benign tumor without known coagulation disorder or ongoing anticoagulation. Preoperative randomization and data management is software-supported (REDCap 9.1.24, Vanderbilt University). Results The study has been approved by the leading ethics committee in 10/2019 and is open since 04/2019. Currently, nine (9) ENT hospitals are participating in the study, 6 of them in Germany and 3 in Austria. Enrollment of patients is ongoing in 7 centers. With a calculated follow-up-to-treat population of 800 test persons, the planned duration of the study is 4 years. Conclusions The Redon-study is the first prospective randomized study worldwide to investigate the effect of a drain in parotidectomy. In order to achieve the recruitment goal within the planned time frame, the participation of further specialized study centers is needed. We also encourage all ENT physicians to make their patients aware of the Redon study, inform them about the possibility of participating in the study and refer them to one of the participating centers

Challenges and opportunities for Multi-National Investigator-Initiated clinical trials for ALS: European and United States collaborations

An inherent challenge to clinical trials that aim to test the efficacy of experimental therapeutics for patients with amyotrophic lateral sclerosis (ALS) is the relative rarity of the disease. A promising solution to this problem is a multi-center approach that ideally includes sites distributed across a broad geographic area. In support of such an approach, the European E-RARE program and the United States National Institutes of Health (NIH) partnered to support the investigator-initiated ROCK-ALS trial (Eudra-CT-Nr.: 2017-003676-31, NCT03792490) as a multi-national collaboration between centers in Europe and North America that is led by European investigators. During the set-up of this international trial, however, a number of unanticipated legal, administrative, and financial complexities emerged that required significant adaptation of the proposed trial scheme. Here, we report our experience navigating these obstacles and describe the potential solutions that we explored. Our experience may inform future efforts to implement multi-national investigator-initiated trials that involve both European and United States centers