Statistical analysis plan for the randomized controlled trial CardioCare MV investigating a novel integrated care concept (NICC) for patients suffering from chronic cardiovascular disease

Abstract

Background: Cardiovascular diseases are the major cause of death globally and represent a major economic burden on health care systems. For patients with heart failure, atrial fibrillation or therapy-resistant hypertension, we have developed a novel integrated care concept (NICC) which combines telemedicine with intensive support by a care center, including a call center, an integrated care network including inpatient and outpatient care providers and guideline therapy for patients (Schmidt et al. 2018 Trials 19:120). Here, we describe challenges and solutions in patient recruitment and provide the statistical analysis plan. Methods: The study CardioCare MV is a prospective, randomized, controlled, parallel-group, open-label, bi-center trial with two groups for comparing NICC with standard of care (SoC). Because of issues with patient enrollment we adapted the study plan after consultation with the Ethics Committee and the funding agency. We altered the analysis strategy for the primary endpoints, which led to a change in the required sample size. We also changed the access points to patients from inpatient hospitals specialized in the treatment of patients with cardiovascular disease to specialized practices. Results: Recruitment of patients started on 1 December 2017, and first patient in was on 4 December 2017. Recruitment was completed on 15 August 2019 as planned according to the amended study plan. The follow-up period will end in August 2020. A total of 964 patients was enrolled into the trial. The statistical analysis plan was finalized prior to last patient in. Results will be available by the end of 2020. Discussion: The trial will inform care providers whether quality of care can be improved by an integrated care concept providing telemedicine through a round-the-clock call center approach. We expect that cost of the NICC will be lower than standard care because of reduced hospitalizations. The trial will guide additional research to disentangle the effects of this complex intervention.

Comparison of telemonitoring combined with intensive patient support with standard care in patients with chronic cardiovascular disease - a randomized clinical trial

“…CardioCare MV was a prospective, randomized, controlled, parallel-group, open-label, blinded-observer trial that aimed to demonstrate NICC’s superiority over SoC according to three hypotheses: (1) NICC is superior to SoC in terms of the combined endpoint comprising mortality, stroke, or myocardial infarction, which should be decreased under NICC versus SoC at 12 month follow-up; (2) NICC results in a lower number of inpatient treatment days versus SoC at 12 month follow-up; (3) NICC results in a lower proportion of patients achieving the combined endpoint of mortality, stroke, myocardial infarction, or cardiac decompensation versus SoC at 12 month follow-up. Details on trial design and statistical analysis plan were formerly reported [ 10 , 11 ].…”

“…Because of slow recruitment, the responsible parties endorsed the following changes: recruitment prolongation until 15th August 2019; inclusion of a further 26 cardiologists/internists as part of the UMR study centre; changes in statistical testing procedures. This amended statistical analysis plan (SAP) was presented to the Data Monitoring Committee (DMC), which approved the changes, as did the Ethics Committee of the Rostock University Medical Faculty, and subsequently published [ 11 ].…”

A Modular Approach to Combine Postmarket Clinical Follow-Up Studies and Postmarket Surveillance Studies

“…Starting point for template development were CIPs developed by the authors. [20][21][22]29 One of the published protocols was used as prototype for developing the CIP template. The authors next expanded the CIP template to a full protocol.…”

“…A.Z. is board-certified trial statistician 19 and has extensively worked on medical devices, including planning [20][21][22] and analysis of randomized controlled trials, 23 methodological work on medical devices, and its regulatory affairs 24,25 and publication recommendations. 26,27 K.K.…”

“…is involved in the quality management of trials for approximately 20 years. Her work includes a doctoral thesis and publications on standard operating procedures (SOPs) for clinical trials, 28 the publication of study protocols, [20][21][22] and methodological work on medical device trials. 25…”