Trial design and participants
KORINNA (“Coronary infarction follow-up in the elderly”) is a single-centre randomized two-armed parallel group trial of patients aged 75 years and older hospitalized with an acute myocardial infarction. The allocation ratio was 1:1.
Deviations from the study protocol include the decrease of minimum age of participants from 75 to 65 years, based on an unexpected low number of older aged persons which became apparent in the first year of recruitment. As a consequence, the study protocol was modified in coordination with the study’s Advisory Board by setting the minimum age of participants to 65 years. The recruitment phase was expanded accordingly. In addition, 11 persons (7 patients in the intervention group and 4 patients in the control group) were excluded because they died or withdrew consent before hospital discharge or did not meet the inclusion criteria. This deviation from the protocol was discussed with, and approved by the study’s Advisory Board.
Patients aged 65 and older who were hospitalized with a first or recurrent myocardial infarction between September 2008 and May 2010 in the Hospital of Augsburg, a tertiary care unit situated in the city of Augsburg, Southern Germany, were included consecutively. Patients who were in institutionalized care or planned to move into institutional care or outside the study region within the next months were excluded. Furthermore, patients with severe comorbidity (e.g. terminal cancer) which was associated with a life expectancy of < 1 year, and patients who were not able to communicate in German language were excluded. Finally, patients who were unable or unwilling to give written informed consent (e.g. patients with dementia) could not be included in the study.
The study protocol was approved by the Ethics Committee at the Bavarian Chamber of Physicians (Date of approval: 11.11.2008, Reference number: 08064). Furthermore, the study was conducted in accordance to German privacy law and in compliance with the Helsinki Declaration. The trial was registered in the Current Controlled Trials database in February 2009. Patients were recruited from 08.09.2008 to 11.05.2010 and one-year follow-up examinations took place from 29.09.2009 to 16.06.2011.
Interventions
The nurse-based intervention is a complex intervention combining components from case-management and disease-management. Case-management elements include the identification of individual care problems and the facilitation of care coordination. Disease-management elements cover the identification of problems regarding management of cardiac risk factors and the provision of information and individual education. Main topics of the intervention were symptoms and management of heart failure (dyspnea, oedema, liquid control, body weight control), symptoms of angina, falls, blood pressure, heart rate, blood glucose, medication and medication adherence, depressed mood, and general physical condition. The selection of intervention’s components is based on the experiences with nurse-based follow-up programs in heart failure patients [15] and AMI patients [16]. It could be demonstrated that individual problem identification and corresponding care coordination and education can be effective measures to reduce readmission and death in CHD patients. Since elderly persons with AMI are more likely to have clinical and social risk factors that need specific consideration, it was expected that they benefit from an individual follow-up care.
Based on an assessment of these potential intervention areas using a structured interview guide, the study nurse estimated the need for an intervention and selected the type of intervention (e.g. referral to the general practitioner, individual education on medication use, contacts to cardiac sports group). For instance, if the patient reported that he/she fell down, the nurse may check the home environment for any trip hazards and may advise on its modification, may examine the patients’ walking abilities and advises on training or supportive devices, or may refer to the general practitioner in order to check possible adverse medication effects. The standards for conducting home visits and telephone calls, including potential interventions for each area, were provided in a standard operating procedures guide which has been developed by a multidisciplinary team consisting of the principal investigators, the study physician and the study nurses. The study nurses received a training on assessments and interventions by the study physician and the principle investigators. The intervention was tested and revised in a pilot phase from 27.06.2008 to 21.07.2008 in 11 patients. During the entire study course a team member joined selected intervention sessions as an observer to get a picture of the guideline adherence and the comparability of the applied interventions among the study nurses. Regular meetings among team members and study nurses were used to discuss problems regarding assessment and intervention and to enhance standardization.
The content and structure of home visits and telephone calls were comparable, and primarily differed regarding location and type of contact between the patient and nurse, and the possibility to perform for example blood glucose and blood pressure measurements.
The study design is shown in Figure 1. Briefly, after giving informed consent, all patients received a baseline assessment during hospital stay shortly before discharge, which was carried out by the study physician and a non-advanced practice study nurse. Those who were subsequently randomized to the intervention group received the intervention starting with the initial session shortly before discharge (for details see [17]).
In this session the patient was provided with information about the disease and comorbidities, about medication and with behavioural recommendations (nutrition, physical activity, smoking etc.). Information was given orally and in written form (so-called “heart book”). A first home visit was arranged 7 to 14 days after discharge, if accepted by the patient, otherwise an appointment for a telephone call was made. If the patient stayed in a rehabilitation hospital immediately after discharge from the Augsburg hospital, the first home visit was postponed accordingly.
Home visits (0 to 4) and telephone calls (at least every 3 months) were carried out according to patient need and patient risk level, which was assessed by the study nurse during the first home visit based on compliance, the social network, and the comorbidities. The risk level classification suggested by Russell et al. [18] was applied. Patients with New York Heart Association (NYHA) Classification class 1 or 2 who showed good compliance and social support were offered only telephone calls whereas for persons with limited compliance and/or social support at least one home visit was scheduled. Participants with NYHA classes 3 or 4 were planned to receive at least 2–3 home visits if they had limitations regarding compliance or social support or no impairments. In case patients with NYHA class 3 or 4 were lacking compliance and social support, at least 4 home visits were scheduled.
Outcomes
The primary endpoint was measured as time between initial hospital discharge and first unplanned readmission to hospital or death. Readmission was defined as admission to any hospital after discharge from the index hospital. Only hospital stays with duration of at least 24 hours were included. In standardized non-interventional telephone interviews performed by study nurses with the patients in both groups at 3, 6, and 9 and 12 months after index hospital discharge patient’s readmissions, acute care visits to physicians, clinics, and ambulatory departments were identified. Self-reported readmissions were validated by hospital records and the study physician decided whether the readmissions were planned or unplanned ones. Blinding of the study physician was maintained. Outcome on all-cause mortality was determined from death certificates, which were obtained from the local health departments. After 12 months a follow-up examination was conducted.
The secondary endpoints of the KORINNA trial comprised clinical parameters such as blood pressure or lipid parameters, as well as functional capacity, nutritional risk, cognitive functioning, depression, and health-related quality of life. Functional ability was assessed using three different questionnaires: the Barthel Index [19], the Health Assessment Questionnaire (HAQ-DI) [20], and the Instrumental Activities of Daily Living Scale (IADL) [21]. Social support was assessed by using a questionnaire (F-sozU) [22], depressive symptoms were assessed by the Geriatric Depression Scale (GDS) [23], emotional well-being by the WHO-5 Well Being Index (WHO-5) [24], and cognitive function was measured by using the Mini Mental State Exam (MMSE) [25]. These instruments are described in more detail elsewhere [17]. The results are already submitted for publication elsewhere.
Another secondary outcome was the estimation of the cost-utility ratio of the case management intervention. Data for the economic analysis was collected by patient report and hospital records. Data on resource utilization was collected quarterly using a self- developed questionnaire based on available instruments such as the RAI (Resident Assessment Instrument) [26] or the RUD (Resource utilization of dementia) [27] and own experiences. Costs for the intervention excluding the costs caused by the study were calculated. Cost components included labor costs, travel expenses, telephone costs etc. In order to calculate quality-adjusted life years (QALYs), the EQ-5D questionnaire [28] was applied at baseline, at interim telephone contacts, and during the final assessment. Moreover, the Visual Analogue Scale (VAS) [28] was applied at baseline and final assessment. A cost-utility-analysis from the societal perspective including the incremental cost-effectiveness ratio (ICER) will be performed. More detailed information on the economic analysis is given elsewhere. The analysis is ongoing and results will be published elsewhere.
Sample size
An event rate (readmission or death) of 40% in the control group was expected based on a comparable study with patients aged 70 years [16]. Our trial was designed to have at least 80% power to detect an improved rate of 25% in the intervention group (i.e. Δ = 0.15) at a two-sided type I error level of 5%. Thus, at least 152 patients per group were needed. We expected a drop-out rate not exceeding 10% during the 1-year follow-up period. In order to allow for loss to follow-up (patient withdrawing consent or moving away from study region), it was planned to recruit a total of 338 patients.
Randomization
A randomization procedure using randomized blocks within strata was applied in order to achieve balanced treatment groups with respect to gender, age (< 70 vs. 70–79 vs. 80+), and number of comorbidities (diabetes and chronic heart failure). In order to ensure the concealment of the allocation, randomization was provided per telephone call to the biostatistical center at the Helmholtz Zentrum München where a randomization list was kept. Blinding of participants was not possible because home visits were only offered for participants from the intervention group. However, the persons who performed the final assessment after 1 year and the person who validated data on readmissions remained blinded towards the patient’s group assignment.
Statistical methods
The primary analyses were conducted according to the intention-to-treat approach. Kaplan Meier curves were used to display the differences between the intervention and the control group regarding the time to event (i.e. till the first unplanned readmission or death). Cox proportional hazards regression was used to quantify the effect of intervention. For adjustment, the variables diabetes, heart failure, age and gender were included as independent variables into the Cox regression models. Subgroup analyses were performed for high risk groups (i.e. subjects aged 75 and above, subjects with diabetes, subjects with at least one comorbid condition) and for sex. As sensitivity analysis, the first six weeks were disregarded (i.e. the observation time started at day 42 after discharge), to approximate the time period since the first home visit.
