Pharmacotherapy Review and Optimization: Impact on Clinical Outcomes, Social Determinants of Health, and Quality of Life Among Polymedicated Lebanese Older Patients in the Primary Healthcare Setting Amidst Crises
| Registry | NCT07866677, acronym PHARMACT-PHC |
|---|---|
| Status | Not yet recruiting |
| Phase | Not applicable |
| Study type | Interventional; randomized, parallel, masking: none, treatment |
| Enrollment | 452 (Estimated) |
| Sponsor | National Institute of Public Health, Clinical Epidemiology, and Toxicology-Lebanon (INSPECT-LB) (Other); collaborators: University Hospital, Toulouse |
| Conditions | Older Adults (65 Years and Older), Polypharmacy (People Under Treatment With 5 or More Drugs), Primary Health Care, Social Determinants of Health (SDOH), Clinical Outcomes, Quality of Life (QOL), Pharmacotherapy Optimization, Intrinsic Capacity, Health Outcomes |
| Interventions | Structured pharmacotherapy optimization, Usual Care (Other) |
| Dates | start 2026-10-01 (estimated), primary completion 2027-08-01 (estimated), completion 2027-08-01 (estimated), first posted 2026-10-08, last updated 2026-10-08 |
| Locations | 1 site in Lebanon |
Related Papers Related Patents Related Grants Related Experts
All trials for Older Adults (65 Years and Older) All trials for Polypharmacy (People Under Treatment With 5 or More Drugs) All trials of Structured pharmacotherapy optimization All trials of Usual Care
Why are the researchers doing this study? Many older adults take five or more medicines every day. Some of these medicines may no longer help them. Some may even cause harm, such as falls, confusion or tiredness. At the same time, a medicine the person needs may be missing.
The researchers want to find out whether a careful review of a person's medicines helps older adults stay well. They will look at intrinsic capacity. This means the physical and mental abilities a person can draw on: memory and thinking, walking and moving, eating well, mood, eyesight and hearing. They will also look at quality of life, daily life, health and social conditions.
This kind of study has not been done before in primary health care centers in Lebanon.
Who can take part?
You may be able to join if you:
* are 65 years old or older
* have been a patient at one of the health centers for at least one year
* take five or more medicines for long-term health problems
* can carry out your daily activities on your own What will happen in the study? About 452 people will join at the primary health care centers of the Order of Malta Lebanon.
A computer will place each person in one of two groups, by chance, like the toss of a coin. About half (226 people) will be in each group:
* In the first group, a pharmacist will go through all of the person's medicines. The pharmacist will use tools made for checking medicines in older people. The pharmacist will then send suggestions to the person's doctor. The doctor decides what to change. No medicine is changed without the doctor's agreement.
* In the second group, people will keep taking the medicines their doctor already prescribed. These medicines are checked in the usual way, which is the same for all patients. They are not checked with tools made for older people.
The study does not test any new or experimental medicine. Every month, when the person comes to pick up their medicines, the pharmacist will check the medicine list. The pharmacist will write down any change and any problem the person reports.
The researchers will check the person's abilities three times: at the start, after three months, and after six months. They will also ask about quality of life, health and social conditions at the start and after six months.
Each person takes part for six months. What are the possible risks and benefits? In both groups, a person's medicines may change during the study. A medicine may be added, stopped or replaced after a review.
Medicines can cause new problems, such as side effects. This can happen with a new medicine. It can also happen with a medicine the person has taken for a long time. The pharmacist asks about such problems every month. Any change to a person's medicines is decided by their own doctor, as in normal care.
People in the study may or may not feel better. The researchers hope the results will help care for older people in Lebanon and in other countries.
What happens after the study? People in both groups keep receiving the usual care of their health center. Taking part does not change a person's right to care. Joining is a free choice. A person can stop at any time, and their care will not change.
Scientific rationale:
Polypharmacy and potentially inappropriate prescribing (PIP) are associated with adverse drug events, drug-drug interactions, prescribing cascades, falls and functional decline in older adults. PIP covers both the use of medications whose risks outweigh their benefits and the omission of clinically indicated therapies. The WHO Integrated Care for Older People (ICOPE) framework reorients geriatric care toward the preservation of intrinsic capacity (IC), defined as the composite of physical and mental capacities an individual can draw upon, across cognition, locomotion, vitality, psychological status and sensory function. Explicit criteria such as STOPP/START allow structured identification of inappropriate medications and prescribing omissions, while implicit approaches grounded in individualized clinical judgment allow decisions to be tailored to patient context and values. The effect of combining both approaches on IC has not been evaluated in a randomized design. In Lebanon, where a rapid demographic transition coincides with economic crisis and sustained pressure on the healthcare system, ICOPE has not been implemented in primary care, IC has not been systematically studied, and pharmacotherapy optimization is not routinely integrated into geriatric care.
Setting and recruitment strategy:
The trial is conducted in the primary health care centers (PHCCs) operated by the Order of Malta Lebanon and distributed across the Lebanese territory. The study is sponsored by the National Institute of Public Health, Clinical Epidemiology and Toxicology-Lebanon (INSPECT-LB), with the Centre Hospitalier Universitaire de Toulouse as collaborating institution.
Recruitment runs in parallel at all sites over a four-month period, which distributes the enrollment burden across centers. Recruitment targets are allocated in proportion to regional population density and center capacity, with larger numbers drawn from the largest centers. Participants are identified on site during routine visits by trained PHCC staff, mainly pharmacists and triage nurses; no telephone-based or remote recruitment is conducted. Eligible individuals are long-standing beneficiaries of their center who attend regularly for medical services including monthly medication refills, which provides repeated and predictable contact points for screening without requiring an additional visit. In 2025, the participating centers served approximately 14,000 unique beneficiaries aged 65 years and over. Screening logs are reviewed per center on a bi-weekly basis by the principal investigator and the co-investigator to monitor recruitment progress.
Assessment schedule:
Data are collected prospectively at the PHCC through face-to-face interviews conducted by trained staff using a standardized questionnaire. The full assessment is administered at baseline (T0) and at six months (T6). At baseline, the following set of information is obtained to capture functional, sociodemographic and clinical characteristics.
Functional status is assessed using the Activities of Daily Living (ADL) and Instrumental Activities of Daily Living (IADL) scales. These serve both as baseline measures and as eligibility confirmation, ensuring that participants are functionally independent; individuals who do not meet the threshold are not included.
Sociodemographic and center-related data include the geographic location of the center, source of referral and duration of attendance, together with age, sex, educational level, marital status, number of children where applicable, living arrangements, caregiver status, breadwinner status, place of residence (urban or rural), household crowding index, housing ownership, employment status and healthcare coverage.
Lifestyle characteristics and clinical parameters are assessed at T0 and T6 and encompass physical activity, sleep duration, sedentary behavior, caffeine intake, smoking, alcohol consumption, vital signs (heart rate, oxygen saturation, systolic and diastolic blood pressure), laboratory results and chronic diseases.
Frailty and sarcopenia are assessed at T0 and T6 using the Fried frailty phenotype and the SARC-F screening tool. Although these measures are typically part of the Step 2 mobility assessment within the ICOPE framework, they are administered to all participants at baseline following Step 1 screening, to ensure comprehensive characterization of functional status.
Medication-related variables at baseline include the number of prescribed chronic medications, the total daily pill burden, a detailed medication list, and medication adherence assessed with the Lebanese Medication Adherence Scale for Primary Healthcare (LMAS-PHC). Throughout the six-month follow-up, the pharmacist updates the medication list at each monthly in-person refill visit, alongside routine counselling and education, and documents any medication change with its reason and any reported adverse event. Adherence is re-assessed with the LMAS-PHC at six months.
Health-related quality of life is evaluated at T0 and T6 with the WHO Quality of Life-OLD brief instrument. Social determinants of health are assessed at the same timepoints using the Socioeconomic Status for Primary Healthcare (SES-PHC) scale, the Steps to Better Health Questionnaire (STBH-Q), the Functional Assessment of Chronic Illness Therapy-Spiritual Well-Being scale (FACIT-Sp-12, version 4), the UCLA Loneliness Scale (ULS-8, version 3) and the European Health Literacy Survey Questionnaire (HLS-EU-Q16).
For data elements that are clinically documented rather than self-reported, such as vital signs, laboratory results, chronic diseases and current medication lists, information may be retrieved from PHENICS, the health information system deployed by the Lebanese Ministry of Public Health across all PHCCs. This minimizes interview burden while ensuring the accuracy and completeness of routinely recorded clinical data.
Implementation of the ICOPE framework:
The ICOPE framework is implemented following a real-life approach. Step 1 screening is systematically performed for all participants across the intrinsic capacity domains defined by WHO: cognition, locomotion, vitality, vision, hearing and psychological status, with vision and hearing forming the sensory domain at the scoring stage. Screening enables early detection of functional decline and supports the assessment of overall intrinsic capacity. It is administered at baseline, at three months (T3) and at six months. The T3 assessment is limited to Step 1 screening; it provides three IC measurements per participant, supports the estimation of individual trajectories, and limits the impact of loss to follow-up before T6.
Step 2 in-depth assessments, using validated tools, are conducted at baseline and at six months, in line with WHO recommendations for biannual evaluation. They are performed selectively, for the domains concerned, and are initiated only after Step 1 alerts have been reviewed and appropriately managed, in order to confirm suspected impairment or screening-detected decline in the corresponding domain. Participants screening abnormal in one or two domains undergo a Step 2 assessment targeted to those domains, while a comprehensive Step 2 evaluation across all domains is undertaken when impairment is identified in at least three domains.
Sample size justification:
The sample size was estimated for the IC endpoint. In the absence of published data in a comparable population, assumptions were derived from preliminary unpublished data from the ongoing INSPIRE study at CHU de Toulouse, France, in which participants aged 65 years and over had a mean IC score of 79.27 (SD 9.47; n = 549), with greater dispersion among those taking five or more medications. A between-group difference of 2.5 IC points (79.0 versus 81.5) was considered clinically plausible, and a conservative standard deviation of 9 points was retained to avoid underestimating variability in an older polymedicated population. With a two-sided alpha of 0.05, 80% power and 1:1 allocation, 203 participants per group were required. To account for an anticipated 10% rate of loss to follow-up, withdrawal of consent and missing primary-outcome data, this figure was inflated by dividing by (1 - 0.10), giving 226 participants per group.
A second, independent estimation was performed to verify the adequacy of this figure under the planned adjusted analysis. Using G*Power (version 3.1.9.7), a multiple linear regression model (fixed model, R² increase) was applied to detect the effect of the pharmacotherapy optimization intervention on IC improvement with adjustment for baseline characteristics. Parameters were set as follows: a small anticipated effect size (f² = 0.02), a two-tailed alpha of 0.05, a power of 0.80, one tested predictor (the intervention) and 30 total predictors accounting for potential confounders, including age, sex, number of medications, comorbidities and baseline intrinsic capacity measures. Under these assumptions, a minimum of 395 participants was required, corresponding to 439 participants after the same 10% inflation.
The two approaches therefore converged on a comparable magnitude, and the larger, more conservative estimate of 452 participants (226 per group) was retained as the recruitment target; at this sample size, the adjusted regression model attains a statistical power of 0.85, providing an additional margin for the multivariable analysis.
Statistical analysis:
Analyses will be performed using SPSS and R, with a two-sided alpha of 0.05 and 95% confidence intervals. Baseline characteristics will be described overall and by arm, without significance testing of between-arm differences. Analyses follow the intention-to-treat principle: all randomized participants from both arms will be analyzed in the group to which they were allocated.
The IC score is the additive ICOPE Step 1 composite score. Each domain is rescaled to 0-100 using the percentage of maximum possible method, and the score is the arithmetic mean of five domains: cognition, locomotion, vitality, sensory capacity (vision and hearing averaged) and psychological status. Step 2 data are not used in the derivation of this score.
The intervention effect on IC will be estimated using a linear mixed-effects model including group, time (T0, T3 and T6) and the group-by-time interaction as fixed effects, participant-specific random intercepts and, if supported by model fit, random slopes for time, adjusted for relevant baseline covariates. The distribution of IC scores by arm will be described in relation to published French age- and sex-specific reference centiles and to preliminary Lebanese centiles. Continuous secondary outcomes will be analyzed using the same mixed-effects approach.
PIP is measured before randomization and is therefore analyzed descriptively: the number and types of PIP identified with the STOPP/START version 3 criteria and an implicit approach will be reported for the full baseline sample and by arm, with correlates examined using multivariable logistic regression for the presence of at least one PIP and multivariable linear regression for the number of PIP per participant. As the intervention effect is tested inferentially only for the IC outcome, no adjustment for multiplicity between the two co-primary outcomes is applied.
No imputation will be performed. Baseline covariates are collected in full, and the likelihood-based mixed-effects models use all available observations under a missing-at-random assumption. Step 2 data not indicated by Step 1 screening are structurally absent by design and are not treated as missing.
Exploratory analyses, conducted where data permit and considered hypothesis-generating, include a bifactor confirmatory factor analysis to derive a latent IC score, retained only if model fit and factor-score reliability are acceptable; preliminary Lebanese age- and sex-specific IC centile curves generated with GAMLSS; IC centile transitions between baseline and six months by arm; time from randomization to first medication change analyzed with Cox proportional hazards regression; psychometric evaluation of the study scales; and domain-level analyses of Step 2 data restricted to participants with impairment identified at screening.
Safety monitoring and trial conduct:
A data monitoring committee of four members, independent of the sponsor, the collaborating institution, the host institution and the funders, reviews the monthly medication review records throughout the trial and meets monthly from the initiation of data collection. No interim analysis is planned, given the six-month follow-up and the profile of the intervention, which involves no novel molecule, no experimental treatment, no placebo and no withholding of indicated care, and in which all prescribing decisions remain the responsibility of the treating physician. Site pharmacists report adverse events to the principal investigator within 24 hours of identification; serious adverse events are reported to the ethics committee in accordance with its requirements. Site visits to the participating centers are conducted every one to two months to verify data quality and protocol compliance; the interval may be extended where road safety or security conditions temporarily prevent travel.
| Arm | Type | Interventions | Description |
|---|---|---|---|
| Structured pharmacotherapy optimization | Experimental | Other: Structured pharmacotherapy optimization | Intervention-group participants at each Order of Malta Lebanon primary health care center (PHCC) will undergo structured pharmacotherapy optimization using the STOPP/START explicit criteria and the implicit prescribing approach, supervised by the research team with support from an expert panel in clinical pharmacy and geriatric pharmacotherapy. Patient cases will be reviewed in weekly meetings between researchers, PHCC pharmacists, and treating physicians, where identified prescribing issues and proposed optimization strategies will be discussed. Final prescribing decisions will remain with the treating physician and his/her clinical judgement, who, after discussing the agreed changes with the patient at the next monthly medication-refill visit, will amend the prescription as clinically appropriate and update it in the health information system. The pharmacist will then provide the participant with the individualized education on the optimized regimen. |
| Usual care | Active comparator | Other: Usual Care | Control-group participants will receive usual care at the participating Order of Malta Lebanon primary health care centers, without the structured pharmacotherapy optimization based on the STOPP/START criteria and the implicit prescribing approach. Usual care comprises multidisciplinary medication reconciliation, routine medication management, patient education and counseling, and dispensing. |
Sex: All, ages: 65 Years to any
Inclusion Criteria: 1. Lebanese patients 2. Older patients ≥ 65 years of age 3. Diagnosed and treated for at least two chronic diseases* 4. Resorting to an OML PHCC and benefiting from chronic medication dispensing services for at least one year 5. Treated with at least five chronic medications 6. Autonomous (non-dependent) patients living in their houses 7. Signed the consent form Exclusion Criteria: 1. Non-Lebanese patients 2. Patients < 65 years of age 3. Patients diagnosed with only one chronic disease 4. Beneficiaries newly registered in the PHCC 5. Patients only presenting to the PHCC for acute consultations and non-chronic medications dispensing services 6. Patients with advanced stage of cognitive impairment 7. Patients diagnosed with cancer 8. Dependent patients or patients residing in specialized care homes/hospitals 9. Persons presenting to the PHCC on behalf of the older patients to collect the monthly medication refill
| Facility | City | Country | Status |
|---|---|---|---|
| Order of Malta Lebanon | Beirut | Lebanon |