The effectiveness of daily SMS reminders in pharmaceutical care of older adults on improving patients’ adherence to antihypertensive medication (SPPA): study protocol for a randomized controlled trial

Background Despite a variety of efficient and cost-effective antihypertensive medication, hypertension remains a serious health and economic burden. High consumption of cardiovascular drugs in the Slovak Republic does result neither in better hypertension control nor in significant decrease in cardiovascular mortality. At the same time, Slovakia has alarmingly low patients’ adherence to medication intake. Studies have shown the efficiency of short messaging service (SMS) reminders to improve patients’ adherence and health outcomes at low costs. Since SMS is popular among Slovaks, this approach may be feasible also in Slovakia. The primary objective is to assess if daily SMS reminders of antihypertensive medication intake provided by pharmacists in addition to the standard pharmaceutical care increase the proportion of adherent older hypertensive ambulatory patients. Methods The SPPA trial is a pragmatic randomized parallel group (1:1) trial in 300 older hypertensive patients carried out in community pharmacies in Slovakia. Trial pharmacies will be selected from all main regions of Slovakia. Trial intervention comprises daily personalized SMS reminders of medication intake embedded into usual pharmaceutical practice. The primary outcome is a combined adherence endpoint consisting of subjective self-reported medication adherence via the eight-item Morisky Medication Adherence Scale (MMAS-8) and objective pill count rate. Secondary outcomes include: change in the MMAS-8; comparison of adherence rates using pill count; change in systolic blood pressure; and patient satisfaction. Also, direct treatment costs will be evaluated and a cost-effectiveness analysis will be carried out. Discussion The SPPA trial engages community pharmacists and mobile health (mHealth) technologies via evidence-based pharmaceutical care to efficiently and cost-effectively addresses current main healthcare challenges: high prevalence of hypertension; overconsumption of cardiovascular medicines; low adherence to medication treatment; and resulting uncontrolled blood pressure. The results may identify new possibilities and capacities in healthcare with low additional costs and high value to patients. Trial registration ClinicalTrials.gov, NCT03105687. Registered on 07 March 2017. Electronic supplementary material The online version of this article (doi:10.1186/s13063-017-2063-8) contains supplementary material, which is available to authorized users.


Trial registration 2a
Trial identifier and registry name.
If not yet registered, name of intended registry page #1 2b All items from the World Health Organization Trial Registration Data Set page #6-#7

Protocol version 3 Date and version identifier page #1
Funding 4 Sources and types of financial, material, and other support page #60 Roles and responsibilities 5a Names, affiliations, and roles of protocol contributors page #3 5b Name and contact information for the trial sponsor page #3 5c Role of study sponsor and funders, if any, in study design; collection, management, analysis, and interpretation of data; writing of the report; and the decision to submit the report for publication, including whether they will have ultimate authority over any of these activities page #3, #60

Methods: Participants, interventions, and outcomes
Study setting 9 Description of study settings (eg, community clinic, academic hospital) and list of countries where data will be collected. Reference to where list of study sites can be obtained

page #27
Eligibility criteria 10 Inclusion and exclusion criteria for participants. If applicable, eligibility criteria for study centres and individuals who will perform the interventions (eg, surgeons, psychotherapists)

Interventions 11a
Interventions for each group with sufficient detail to allow replication, including how and when they will be administered page #32 -#35 11b Criteria for discontinuing or modifying allocated interventions for a given trial participant (eg, drug dose change in response to harms, participant request, or improving/worsening disease)

page #33 -#34
11c Strategies to improve adherence to intervention protocols, and any procedures for monitoring adherence (eg, drug tablet return, laboratory tests)

N/A
Improving adherence is the main purpose of the trial 11d Relevant concomitant care and interventions that are permitted or prohibited during the trial page #34 Outcomes 12 Primary, secondary, and other outcomes, including the specific measurement variable (eg, systolic blood pressure), analysis metric (eg, change from baseline, final value, time to event), method of aggregation (eg, median, proportion), and time point for each outcome. Explanation of the clinical relevance of chosen efficacy and harm outcomes is strongly recommended page #36 -#40 Participant timeline 13 Time schedule of enrolment, interventions (including any run-ins and washouts), assessments, and visits for participants. A schematic diagram is highly recommended (see Figure) page #46 Sample size 14 Estimated number of participants needed to achieve study objectives and how it was determined, including clinical and statistical assumptions supporting any sample size calculations page #44

Recruitment 15
Strategies for achieving adequate participant enrolment to reach target sample size page #45

Methods: Assignment of interventions (for controlled trials)
Allocation: Sequence generation 16a Method of generating the allocation sequence (eg, computer-generated random numbers), and list of any factors for stratification. To reduce predictability of a random sequence, details of any planned restriction (eg, blocking) should be provided in a separate document that is unavailable to those who enrol participants or assign interventions

page #41
Allocation concealment mechanism 16b Mechanism of implementing the allocation sequence (eg, central telephone; sequentially numbered, opaque, sealed envelopes), describing any steps to conceal the sequence until interventions are assigned

page #41
Implementation 16c Who will generate the allocation sequence, who will enrol participants, and who will assign participants to interventions page #41 -#42 Blinding (masking) 17a Who will be blinded after assignment to interventions (eg, trial participants, care providers, outcome assessors, data analysts), and how 20c Definition of analysis population relating to protocol non-adherence (eg, as randomised analysis), and any statistical methods to handle missing data (eg, multiple imputation) page #52

Methods: Monitoring
Data monitoring 21a Composition of data monitoring committee (DMC); summary of its role and reporting structure; statement of whether it is independent from the sponsor and competing interests; and reference to where further details about its charter can be found, if not in the protocol.
Alternatively, an explanation of why a DMC is not needed 21b Description of any interim analyses and stopping guidelines, including who will have access to these interim results and make the final decision to terminate the trial no interim analysis is planned-page #52

Harms 22
Plans for collecting, assessing, reporting, and managing solicited and spontaneously reported adverse events and other unintended effects of trial interventions or trial conduct page #57 Adverse Events reports: page #46, #48 Auditing 23 Frequency and procedures for auditing trial conduct, if any, and whether the process will be independent from investigators and the sponsor page #56

Research ethics approval 24
Plans for seeking research ethics committee/institutional review board (REC/IRB) approval page #58

Protocol amendments 25
Plans for communicating important protocol modifications (eg, changes to eligibility criteria, outcomes, analyses) to relevant parties (eg, investigators, REC/IRBs, trial participants, trial registries, journals, regulators)

page #58
Consent or assent 26a Who will obtain informed consent or assent from potential trial participants or authorised surrogates, and how (see Item 32)

page #59
26b Additional consent provisions for collection and use of participant data and biological specimens in ancillary studies, if applicable N/A no biological specimen collected

Confidentiality 27
How personal information about potential and enrolled participants will be collected, shared, and maintained in order to protect confidentiality before, during, and after the trial page #50

Declaration of interests 28
Financial and other competing interests for principal investigators for the overall trial and each study site

page #60
Access to data 29 Statement of who will have access to the final trial dataset, and disclosure of contractual agreements that limit such access for investigators page #50-#51 Plans for collection, laboratory evaluation, and storage of biological specimens for genetic or molecular analysis in the current trial and for future use in ancillary studies, if applicable N/A no biological specimen collected *It is strongly recommended that this checklist be read in conjunction with the SPIRIT 2013 Explanation & Elaboration for important clarification on the items. Amendments to the protocol should be tracked and dated. The SPIRIT checklist is copyrighted by the SPIRIT Group under the Creative Commons "Attribution-NonCommercial-NoDerivs 3.0 Unported" license.