**Background:** Multimorbidity—the cooccurrence of multiple chronic diseases—is highly prevalent in general practice, with prevalence ranging from 12.9% in adults aged 18+ to 95.1% in those aged 65+. Multimorbid patients face functional difficulties, polypharmacy, treatment burden, fragmentation of care, reduced quality of life, and increased healthcare utilization. In Germany, GP consultation time is less than 10 minutes, and there were 3,300 unfilled primary care positions in 2019, projected to reach approximately 11,000 by 2035. Advanced practice nurses (APNs) have been successfully integrated into primary care in other countries, with evidence showing equally good or better outcomes compared with GPs. However, APNs are not deployed in German general practices due to historical lack of master's-level education programs, which now exist.
**Methods:** This is a prospective multicentre mixed methods nonrandomized controlled trial conducted in nine general practices in rural Rhineland-Palatinate, Germany. The intervention group (n=817) receives APN-integrated care for 12 months, while the control group (n=1634) receives standard care, matched at a 1:2 ratio on age, sex, comorbidity, and nursing home residence. Inclusion criteria: age ≥18 years, medical diagnosis of at least three chronic diseases leading to GP treatment in at least three of four quarters in the past 12 months, and statutory health insurance. Exclusion: life expectancy <12 months per treating physician.
APNs must hold a professional nursing licence, have ≥2 years nursing experience, a master's-level academic degree, and complete 500 hours of project-specific training. Their tasks include in-depth assessment (cognitive function via DemTect, nutritional status via MNA, pain via NRS and PDI, mobility via DEMMI, psychosocial status via MILVA, and functional status via HAQ), development and monitoring of person-centred care plans, establishing supportive networks, and intensifying communication among care providers. Weekly case conferences with GPs are scheduled. Initial assessment lasts approximately 1.5 hours; follow-up contacts occur every four weeks on average, lasting approximately 30 minutes.
The primary endpoint is the number of emergency contacts per patient within one year (on-call medical service, GP contacts outside office hours, unplanned hospital admissions). Secondary endpoints include use of continuing care institutions, hospital readmission, GP home visits, treatment costs, health status, and satisfaction. Sample size calculation assumed 2.7 emergency contacts per patient per year could be reduced by 15% to 2.295, with alpha=0.05, 80% power, accounting for cluster effect and 30% dropout.
Statistical analysis uses Poisson regression for primary and secondary endpoints comparing intervention and control groups. Cost analysis compares total and subgroup costs from the social health insurance perspective. Qualitative data from interviews with GPs (n=5 for saturation, all 9 targeted), APNs (n=5 for saturation, all 9 targeted), and patients (n=30) will be analysed using content analysis. Internal evaluation uses descriptive and analytical statistics (variance analysis, t-test, Mann-Whitney U test, Wilcoxon test) comparing t0 and t1 measurements.
**Key Results:** This is a study protocol; no results are reported. The trial was registered on 2021/09/06 (DRKS00026172), with first enrolment on 2021/10/01. Target sample size is n=2451. Recruitment status was reported as recruiting.
**Clinical Implications:** If successful, this model could address the GP shortage in Germany by delegating multimorbidity management to APNs, potentially reducing emergency contacts and healthcare costs while maintaining or improving patient outcomes. The study addresses a critical gap in German primary care, where APNs are not currently deployed. Challenges include the political and strategic environment and achieving the planned number of participants. Results will inform policy-makers and healthcare providers about the feasibility and effectiveness of integrating APNs into German general practices.