Nurse-led intervention to improve medication adherence in older adults with hypertension in primary care

ISRCTN	ISRCTN35559821
DOI	https://doi.org/10.1186/ISRCTN35559821
Ethics committee reference number	PI_2023/92
Sponsor	Department of Health of the Government of Navarra (Spain)
Funder	Department of Health of the Government of Navarra (Spain)

Submission date: 01/01/2026
Registration date: 02/01/2026
Last edited: 19/08/2026

Recruitment status: No longer recruiting
Overall study status: Ongoing
Condition category: Circulatory System

Prospectively registered

Protocol

Statistical analysis plan

Results

Individual participant data

Record updated in last year

Plain English summary of protocol

Not provided at time of registration

Contact information

Dr Alcibiades Segundo Diaz Vera
Principal investigator, Public, Scientific

AV. PIO XII, 6, 6 A
Pamplona
31007
Spain

ORCID ID	0000-0002-3715-1713
Phone	+34 (0)617321081
Email	as.diaz.vera@navarra.es

Study information

Primary study design	Interventional
Allocation	Randomized controlled trial
Masking	Open (masking not used)
Control	Active
Assignment	Parallel
Purpose	Health services research, Prevention, Treatment
Scientific title	Efficacy of the implementation of a nurse-led adherence protocol in older patients with hypertension in primary care centres
Study acronym	NURSE-ADHERE-HTN
Study objectives	Current study objectives as of 19/08/2026: The primary objective is to evaluate whether a nurse-led multidimensional educational and behavioural intervention improves adherence to antihypertensive treatment at 6 months, compared with usual care, among adults aged 60 years or older with hypertension in primary care. Adherence will also be assessed at 12 months to determine whether any intervention effect observed at 6 months is maintained over time. Secondary objectives are to evaluate the effects of the intervention on 24-hour ambulatory blood pressure, health-related quality of life, cardiovascular-related emergency department visits and hospital admissions, symptoms of anxiety and depression, adherence to the Mediterranean diet and physical activity; to examine reasons and patterns of non-adherence, medication burden, anthropometric and selected laboratory variables; to explore sociodemographic and clinical factors associated with adherence to antihypertensive treatment; to assess the association between symptoms of anxiety and depression and adherence to antihypertensive treatment; to assess concordance between adherence measured using the MMAS-4 and adherence estimated from electronic prescription dispensing records; and to explore whether intervention effectiveness differs by sex. _____ Previous study objectives: The primary objective is to evaluate whether a nurse-led mixed educational and behavioural intervention improves medication adherence compared with usual care in adults aged 60 years and older with hypertension in primary care. Secondary objectives are to assess the effect of the intervention on blood pressure control, health-related quality of life, and use of healthcare services (emergency department visits and hospital admissions) at 6 and 12 months; to explore sociodemographic and clinical factors associated with medication adherence, including sex-specific differences; to screen for symptoms of anxiety and depression using the Goldberg Anxiety and Depression Scale; and to evaluate whether the effectiveness of the nurse-led intervention on medication adherence, health-related quality of life, and cardiovascular morbidity outcomes (emergency department visits and hospital admissions) at 6 and 12 months differs by sex/gender (effect modification analysis). An additional secondary objective is to explore the association between symptoms of anxiety and depression and medication adherence.
Ethics approval(s)	Approved 23/08/2023, Navarra Clinical Research Ethics Committee (CEIm) (Irunlarrea Street, 3, Pamplona, 31008, Spain; +34 (0)848 42 24 95; ceicnavarra@navarra.es), ref: PI_2023/92
Health condition(s) or problem(s) studied	Arterial hypertension
Intervention	Current interventions as of 19/08/2026: Randomisation was performed at the primary care centre level (cluster randomisation). The 14 participating primary care centres were centrally allocated in a 1:1 ratio to either the intervention group or the usual-care control group, with seven centres per group. Two nurses participate at each centre, and all participants recruited within the same centre receive the allocation assigned to that centre. The allocation sequence was generated centrally using a computer-generated random sequence by an independent researcher who was not involved in participant recruitment or intervention delivery. Because of the nature of the intervention, participating nurses and patients are not blinded to group allocation. Both groups undergo the same standardised outcome assessments. For the prespecified statistical analysis, the study groups will be coded as A and B, and the analysts will remain blinded to group identity until completion of the primary analysis. The intervention is a nurse-led multidimensional educational and behavioural programme delivered in primary care. Before study initiation, nurses delivering the intervention attended a standardised 6-hour face-to-face training session conducted over one morning. Training covered medication adherence, motivational interviewing, antihypertensive pharmacotherapy, the Mediterranean diet, healthy lifestyles, physical activity, intervention materials and standardised study procedures. The intervention comprises: Individualised education on hypertension, cardiovascular risk and antihypertensive treatment. A structured motivational interview to identify barriers to adherence to antihypertensive treatment and agree on individualised adherence-support strategies. Review of the antihypertensive treatment regimen, medication-taking routines, dosage schedules and practical barriers. Individualised Mediterranean-diet and physical-activity counselling supported by standardised educational materials and weekly exercise programmes. Each participant allocated to the intervention group receives an elastic resistance band. Recommendations are tailored according to the participant’s clinical characteristics, comorbidities and previous level of physical activity. Two telephone reinforcement contacts planned during the 12-month follow-up period. Physiotherapy support and pre-existing physical-activity promotion programmes are available at all seven intervention centres. All face-to-face intervention sessions are conducted at the participating primary care centres; home visits are not part of the intervention. The structured medication-adherence component focuses specifically on antihypertensive treatment. Participants in the control group receive usual care and do not receive the structured multidimensional intervention. Both study groups are followed for 12 months. _____ Previous interventions: Randomisation will be performed at the level of the nursing professional (cluster randomisation). Within each participating primary care centre, nurses will be randomly allocated in a 1:1 ratio to either the intervention group or the control group (usual care). All eligible patients under the care of each nurse will be assigned to the same study arm as their nurse. The randomisation sequence will be generated centrally using a computer-generated random allocation sequence. Due to the nature of the intervention, blinding of nurses and patients is not feasible; however, outcome assessment will be performed using standardised instruments and routinely collected clinical data. A nurse-led mixed educational and behavioural intervention delivered in primary care, consisting of: 1. Training of nursing professionals in medication adherence and motivational interviewing 2. Structured motivational interview with patients 3. Systematic medication review 4. Lifestyle counselling (diet, physical activity, smoking, alcohol) 5. Reinforcement through telephone calls and home visits Duration of patient follow-up: 12 months
Intervention type	Mixed
Primary outcome measure(s)	Current primary outcome(s) as of 19/08/2026: Adherence to antihypertensive treatment measured using the 4-item Morisky Medication Adherence Scale (MMAS-4), maintaining the licensed wording, structure and standardised scoring method at baseline, 6 months (primary endpoint) and 12 months (assessment of maintenance of the intervention effect) _____ Previous primary outcome(s) as of 29/05/2026: 1. Medication adherence measured using the 4-item Morisky Medication Adherence Scale (MMAS-4), maintaining the original validated wording, structure, and standardized scoring method at baseline, 6 months and 12 months _____ Previous primary outcome(s): 1. Medication adherence measured using Morisky–Green questionnaire at baseline, 6 months and 12 months
Key secondary outcome measure(s)	Current key secondary outcome(s) as of 19/08/2026: 1. Ambulatory blood pressure measured using 24-hour ambulatory blood pressure monitoring with the Microlife WatchBP O3 AFIB (BP3SZ1-1), recording mean systolic and diastolic blood pressure for the overall 24-hour period and for the daytime and night-time periods at Baseline, 6 months and 12 months 2. Health-related quality of life measured using the EQ-5D-3L descriptive system and EQ Visual Analogue Scale (EQ-VAS) at baseline, 6 months and 12 months 3. Symptoms of anxiety and depression measured using the Goldberg Anxiety and Depression Scale (GADS) at baseline, 6 months and 12 months 4. Cardiovascular-related emergency department visits measured using electronic health records at baseline, 6 months and 12 months 5. Cardiovascular-related hospital admissions measured using electronic health records at baseline, 6 months and 12 months 6. Adherence to antihypertensive treatment estimated from dispensing records measured using electronic prescription dispensing records, comparing the number of antihypertensive tablets dispensed with the number prescribed during the preceding 180 days, at baseline, 6 months and 12 months 7. Maintenance of the intervention effect on adherence to antihypertensive treatment measured using the 4-item Morisky Medication Adherence Scale (MMAS-4), maintaining the licensed wording, structure and standardised scoring method, at 12 months 8. Adherence to the Mediterranean diet measured using the Mediterranean Diet Adherence Screener (MEDAS) at baseline, 6 months and 12 months 9. Physical activity measured using the International Physical Activity Questionnaire (IPAQ) at baseline, 6 months and 12 months 10. Reasons and patterns of non-adherence to antihypertensive treatment measured using the self-reported EFNA questionnaire at baseline, 6 months and 12 months 11. Anthropometric measurements measured using weight, height, body mass index and waist circumference at baseline, 6 months and 12 months 12. Selected laboratory variables measured using laboratory test results obtained from electronic health records, including haematocrit or haemoglobin, glucose, glycated haemoglobin, total cholesterol, high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, triglycerides, potassium, sodium, uric acid, creatinine, estimated glomerular filtration rate, calcium, urinary albumin-to-creatinine ratio and microalbuminuria at baseline, 6 months and 12 months 13. Medication burden measured using the total number of prescribed medications recorded in the electronic health record at baseline, 6 months and 12 months 14. Concordance between adherence measures measured using agreement between adherence assessed using the 4-item Morisky Medication Adherence Scale (MMAS-4) and adherence estimated from electronic prescription dispensing records at baseline, 6 months and 12 months _____ Previous key secondary outcome(s): 1. Blood pressure control measured using office blood pressure measurement at baseline, 6 months and 12 months 2. Health-related quality of life measured using EuroQol-5D at baseline, 6 months and 12 months 3. Symptoms of anxiety and depression measured using Goldberg Anxiety and Depression Scale at baseline, 6 months and 12 months 4. Cardiovascular-related emergency department visits measured using electronic health records at baseline, 6 months and 12 months 5. Cardiovascular-related hospital admissions measured using electronic health records at baseline, 6 months and 12 months 6. Medication adherence measured using pharmacy refill data (electronic prescription records) at baseline, 6 months and 12 months These outcomes (blood pressure control, health-related quality of life, cardiovascular-related emergency department visits and hospital admissions, and medication adherence based on pharmacy refill data) will also be analysed to evaluate whether the effectiveness of the intervention differs by sex/gender (effect modification analysis).
Completion date	31/08/2027

Eligibility

Participant type(s)
Age group	Mixed
Lower age limit	60 Years
Upper age limit	120 Years
Sex	All
Target sample size at registration	280
Key inclusion criteria	Current key inclusion criteria as of 29/05/2026: 1. Age ≥60 years 2. Diagnosis of arterial hypertension 3. Prescribed antihypertensive medication 4. Non-adherence according to the MMAS-4 standardized scoring method 5. At least one primary care visit in the previous year 6. Written informed consent _____ Previous key inclusion criteria: 1. Age ≥60 years 2. Diagnosis of arterial hypertension 3. Prescribed antihypertensive medication 4. Non-adherence (Morisky–Green score ≥1) 5. At least one primary care visit in the previous year 6. Written informed consent
Key exclusion criteria	Current key exclusion criteria as of 19/08/2026: 1. Institutionalised patients 2. Life expectancy of less than 12 months 3. Cognitive or physical conditions preventing participation or completion of the study procedures _____ Previous key exclusion criteria: 1. Institutionalised patients 2. Life expectancy <12 months 3. Cognitive or physical conditions preventing participation
Date of first enrolment	09/02/2026
Date of final enrolment	23/08/2026

Locations

Countries of recruitment

Spain

Study participating centres

Results and Publications

Individual participant data (IPD) Intention to share	No

Editorial Notes

19/08/2026: The following changes were made to the study record:
1. The study objectives were changed.
2. The study design was changed from Blinded (masking used) to Open (masking not used).
3. The interventions were changed.
4. The key exclusion criteria were changed.
5. The primary outcome(s) were changed.
6. The key secondary outcome(s) were changed.
29/05/2026: The following changes were made to the study record:
1. The primary outcome(s) were changed.
2. The key inclusion criteria were changed.
25/02/2026: The following changes were made to the study record:
1. The date of first enrolment was changed from 01/04/2026 to 09/02/2026.
2. The completion date was changed from 30/12/2026 to 31/08/2027.
3. The Control was corrected from Historical to Active.
24/02/2026: The following changes were made:
1. Final enrolment number (320) was removed.
2. Date of first enrolment was changed from 23/08/2023 to 01/04/2026.
05/01/2026: The secondary outcomes were updated.
02/01/2026: Study's existence confirmed by the Navarra Clinical Research Ethics Committee (CEIm).