Clinical Trial Details
— Status: Enrolling by invitation
Administrative data
| NCT number |
NCT05307666 |
| Other study ID # |
Pro00089227 |
| Secondary ID |
|
| Status |
Enrolling by invitation |
| Phase |
Phase 4
|
| First received |
|
| Last updated |
|
| Start date |
July 28, 2022 |
| Est. completion date |
September 30, 2024 |
Study information
| Verified date |
August 2023 |
| Source |
University of Alberta |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Interventional
|
Clinical Trial Summary
Many health care providers believe "less-is-more" for older adults, and evidence suggests
minimizing certain medications might improve health outcomes. While this evidence focuses on
specific medications believed potentially problematic for seniors, it is really adverse
reactions to COMMON medications (e.g. medications lowering blood sugar or treating pain) that
bring older adults to emergency departments.
Knowing recommended drug doses are lower in seniors, and knowing most adverse drug reactions
are dose-related, the investigators are organizing primary care providers (family physicians
and nurse practitioners) to invite their patients 80 years and older on 6 or more medications
to review with them whether some medications could be safely reduced.
For drugs treating a symptom (e.g. heartburn), patients and providers will work together to
find the lowest dose that provides the same benefit. For drugs that lower blood pressure or
blood sugar, doses will be adjusted to keep blood pressure and blood sugar in the upper end
of the target range, a range many providers feel to be safer for older adults.
Each provider will invite half their eligible patients to a minimization visit at the start
of the study, and invite the other half later - after the health effects of minimizing the
early group's medications is assessed. To do this, investigators will compare early
minimizers to those whose medicines have not yet changed using electronic health data
routinely collected on all Albertans. We hypothesize that minimizing medications will prolong
independence, reduce mortality and hospitalization, and improve quality of life.
It is important to recognize that the intervention (reviewing all medications and determining
the lowest effective doses) is already widely recommended as best practice when prescribing
for older adults. Despite this however, such medication reviews only infrequently take place.
In this study investigators hope to demonstrate that family physicians can minimize their own
prescribing, and that organizing providers in a way that permits such reviews to take place
can provide health benefits to patients.
Description:
PURPOSE
To organize primary care providers, and their older patients with polypharmacy, in a way that
permits them to collaboratively determine the lowest effective dose of all amenable
medications. And, in so doing, to provide randomized controlled trial evidence as to whether
minimizing medication doses improves health outcomes in this population.
HYPOTHESIS
1. Primary care providers can easily reduce medication doses in their own patients when
organized appropriately to do so.
2. Determining and utilizing the minimum effective dose of all medications will prolong
independence, reduce hospitalization, and potentially prolong life.
JUSTIFICATION
A) THE PROBLEM
The number of medications used to treat chronic conditions increases with age. "Polypharmacy"
is said to be present when the number of daily medications is high, although the threshold to
meet that definition (e.g. ≥6 daily medications) is not universally agreed upon.
According to data provided by Alberta Health Services (AHS), 62.2% of community-dwelling
Albertans ≥80 yrs (74,525 individuals as of Dec 31, 2016) renew 6 or more medications
annually. Many such individuals are frail, and virtually all have multiple chronic conditions
that place them at high risk of adverse health events - events that can threaten their
independence.
The potential for adverse drug-drug and drug-disease interactions increases exponentially
with each additional co-morbidity, and each additional medication. Although prescribed for
good reasons, all medications have potential for adverse effects. This is especially true for
seniors, who are more susceptible to adverse drug effects, in whom adverse drug effects may
go unrecognized, and in whom these drugs are seldom studied (only 7% of cardiovascular trial
participants are over 75).
Polypharmacy is associated with disturbances of balance, and deterioration of gait (walking
ability). Observational studies that control for comorbidity (the presence of various health
conditions) additionally show the number of daily medications to be associated with falls,
fractures, adverse drug events, all-cause hospitalization, cognitive impairment, diminished
physical function (e.g. ability to cook or clean for yourself), and death. Conceivably, if
such associations are causal, reducing the number of medications (termed "deprescribing")
might reduce the cost of care while simultaneously improving quality of care, potentially
prolonging independence, delaying mortality, and improving a sense of well-being.
B) THE SOLUTION
BACKGROUND: Efforts to reduce polypharmacy typically 1) focus on stopping drugs deemed
potentially inappropriate for seniors, and 2) employ external experts (e.g. pharmacists or
geriatricians) to evaluate medications and make recommendations to the primary care provider.
Although these are undoubtedly valuable reviews, the number of medications stopped following
such an intervention is not large. Cochrane systematic review suggests five patients must be
reviewed to stop one potentially inappropriate drug, in one patient. However, the vast
majority of emergency room visits for adverse drug events are for COMMONLY USED MEDICATIONS
that are NOT deemed potentially inappropriate (e.g. glucose lowering medications, opioids,
anticoagulants, antihypertensives). Potentially inappropriate drugs make up only 3.4% of such
presentations.
A NEW PERSPECTIVE: Most adverse drug reactions are dose-related, the optimal dose of most
mediations is lower in seniors, and 2/3 of older adults want to reduce their medications. A
simple evidence-based approach that appropriately MINIMIZES (e.g. reduces by 50%) doses of
ALL amenable medications in older adults may do more to reduce adverse drug events than
targeting the subset of potentially inappropriate medications for discontinuation.
AN UNRECOGNIZED OPPORTUNITY: Relying on external experts to review medication lists is not
readily scalable without significant cost. It also produces little change in medications
since the usual care provider often declines the changes, citing patient context and history
not available to the reviewer. If a mechanism existed to enable primary care providers to
rationalize/minimize THEIR OWN PRESCRIBING, it would be far more cost-effective and
spreadable.
PILOT DATA: To determine if family physicians can reduce their own prescribing, the
investigators organized 2 large clinics to present medication profiles for 44 randomly
selected patients (≥80 yrs with ≥6 daily medications) to each patient's provider (14 family
physicians, 1-5 patients/physician). These physicians identified 25.2% of medications as
potentially reducible or stoppable if patients wanted that and came in for medication review.
This compares to 2.5% of medications being stopped (albeit potentially inappropriate
medications) in conventional deprescribing trials.
THE TRIAL: The investigators intend to implement organizational changes that will enable
primary care providers to focus on minimizing/rationalizing the prescribing of all
medications in their older polypharmacy patients - something widely recommended as good
geriatric prescribing practice. The intention is to do this in over 150 primary care
practices spread widely across Alberta, and use administrative claims data to assess
differences in patient-oriented outcomes (e.g. all-cause death, nursing home admission)
between those receiving early versus delayed targeting for medication minimization.
OBJECTIVES
1. To determine, for older adults with polypharmacy, whether a medication review by their
own primary care provider, will lead to lower medication dosages.
2. To determine, for older adults with polypharmacy, whether lower medication doses will
result in better health outcomes.
RESEARCH METHOD/PROCEDURES
Setting: "Real-World" primary care clinics widely distributed across Alberta.
Population: All community dwelling adults (no exclusions) ≥80 years of age using ≥6 longterm
medications.
Design: Parallel randomized controlled trial with patient level randomization. No
stratification or blocking, however eligible patients with the same residence (likely to be
spouses) will be allocated to the same study arm to minimize confounding.
Intervention: Workflow efficiencies enabling patients and their usual primary care provider
to work together on minimizing medication dosages - i.e. advising providers of eligible
patients, arranging minimization specific visits, "brown-bag" review of medications,
symptom-driven minimization, and adding a lower limit to the target range for blood pressure
(e.g. systolic BP 130-140 mmHg), and blood sugar (e.g. HbA1c 7.5-8.0).
Comparator: Usual care
Outcomes:
All outcomes are derived from administrative claims data that are collected, accessed, and
analyzed by Alberta Health Services (Alberta Provincial Government). Specific outcomes are
listed below.
STUDY FLOW:
1. IDENTIFYING/ENGAGING PROVIDERS: The principal investigator, and other family physician
co-investigators, will continually recruit practices to participate in MinMed. Most
participating practices will be affiliated with the Pragmatic Trials Collaborative
(www.PragmaticTrials.ca), with new practices being recruited by word of mouth, and
through presentations at continuing medical education events.
2. IDENTIFYING PATIENTS: AHS Provincial Research Data Services will identify all patients
≥80yrs with ≥6 longterm medications attending each participating provider, and give
those providers, randomly determined, the names of HALF their eligible patients to work
with ("early" minimization group), delaying the other half (comparison group) until
study completion. Patients sharing a home address (often spouses) receive the same
allocation. Longterm medications are defined as those dispensed ≥2 times in the
preceding 200 days.
3. INVITING PATIENTS: Providers will receive, for each early-minimization patient, one
un-addressed postage-paid envelope containing a letter of invitation to a medication
minimization visit. Provider offices will attach mailing labels, and mail these
envelopes. Interested patients make a provider appointment and bring with them all pill
bottles. Provider offices make follow-up phone-calls to letter non-responders to confirm
whether or not they are interested in participating.
4. MINIMIZING MEDICATIONS: Providers follow 2 simple rules: 1) For medications treating a
symptom, work collaboratively with patients to find the lowest effective dose and
consider reducing by ¼ or ½ dose every few weeks to get there; and 2) For drugs treating
blood pressure or blood sugar - introduce lower limits to BP and HbA1c that are 10mmHg
lower than the intended BP target (e.g. targeting 130-140mmHg instead of <140mmHg), and
0.5 units lower than the intended HbA1c target (e.g. 7.5-8.0 instead of <8.0). This
permits compliance with guidelines but avoids unnecessarily low values. Booking visits
specifically for drug review are critical to enabling this process, given such reviews
seldom occurs during time-pressured problem-focused visits. Bringing all pill bottles to
the visit ("brown bag" review) also allows providers to see what patients are actually
taking, and clarifies discussions around specific medications and what to change.
5. FUTILITY ANALYSIS: After the patients of 20 practices have undergone 6 months follow-up
investigators will analyze the process outcomes. If, on average, fewer than 10% of oral
medications have a 50% or better reduction in the number of milligrams dispensed then we
will 1) interview participating providers who have completed their reviews to gather
insight into barriers and facilitators of medication minimization, 2) discuss amongst
co-investigators whether there are process improvements which could be implemented to
improve the minimization process, and 3) discuss whether the observed differences in
medication use are clinically important enough to warrant continuation of the trial (if
not, the trial will break early and report it's process outcomes).
6. EXAMINING PRIMARY / SECONDARY / SAFETY / COST OUTCOMES: The primary clinical outcome is
a composite of all-cause death and admission to nursing home. Once 300 such events are
observed, the study will break and evaluate implementation, clinical, and cost outcomes
using administrative claims data. An Independent Data Safety Monitoring Board (organized
by UBC's Therapeutics Initiative) will evaluate data mid-study (after 150 events) to
ensure no signals of harm. If p is ≤ 0.001 for benefit (the Haybittle-Peto boundary -
recommended to reduce the chance of stopping too early and magnifying benefit), or if p
is ≤ 0.05 for harm, the DSMB will apply clinical judgement and make recommendations to
the steering committee on whether the trial should break early.
PLAN FOR DATA ANALYSIS
All data analysis will be conducted by AHS data analysts. At no time will the investigators
view or receive identifiable patient level data. Only the analysts/programmers working for
the data steward, and the care providers, will know who the participants are.
Most primary / secondary / safety outcomes will be analyzed by Cox proportional hazards
survival analysis or multiple linear regression utilizing covariates predictive of the
outcome of interest. These covariates will be analysis specific, and pre-identified in an
upcoming protocol publication.
