Personalized Patient Data and Behavioral Nudges to Improve Adherence to Chronic Cardiovascular Medications

NCT ID: NCT03973931

Last Updated: 2025-04-02

Study Results

Results available

Outcome measurements, participant flow, baseline characteristics, and adverse events have been published for this study.

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Basic Information

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Recruitment Status

COMPLETED

Clinical Phase

NA

Total Enrollment

9501 participants

Study Classification

INTERVENTIONAL

Study Start Date

2019-07-01

Study Completion Date

2023-11-19

Brief Summary

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The study plans to learn if sending different text messages, serving as reminders or encouragement, may help patients take their medication more often if they have had trouble keeping up with their medicines.

Detailed Description

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Background: Up to fifty percent of patients do not take their cardiovascular medications as prescribed resulting in increased morbidity, mortality, and healthcare costs. Mobile and digital technologies for health promotion and disease self-management offer an intriguing and as of yet untested opportunity to adapt behavioral 'nudges' using ubiquitous cell phone technology to facilitate medication adherence.

Objectives: Aim 1: Conduct a pragmatic patient-level randomized intervention across three health care systems (HCS) to improve adherence to chronic CV medications. The primary outcome will be medication adherence defined by the proportion of days covered (PDC) using pharmacy refill data. Secondary outcomes include clinical events (e.g., event times for stroke, MI, mortality), utilization of care (e.g., hospitalizations or clinic visits for CV-related reasons), and costs of healthcare utilization. Aim 2: Evaluate the intervention using a mixed methods approach and applying the RE-AIM (reach, effectiveness, adoption, implementation, and maintenance) framework. In addition, assess the context and implementation processes to inform local tailoring, adaptations and modifications, and eventual expansion of the intervention within the 3 HCS more broadly and nationally.

Setting: The study will be conducted within three HCS in metro Denver: VA Eastern Colorado Health Care System (VA), Denver Health and Hospital Authority, and UCHealth.

Conditions

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Cardiovascular Diseases Adherence, Medication Medication Adherence Diabetes Mellitus Hypertension Hyperlipidemias Coronary Artery Disease Atrial Fibrillation

Study Design

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Allocation Method

RANDOMIZED

Intervention Model

PARALLEL

The study will be a pragmatic, randomized controlled study with four treatment arms. Once patients are identified through pharmacy refill data to have a 7-day gap in any prescribed CV medication refills, they will be randomized to one of four arms, described in Intervention below. Randomization will be stratified within each of the clinics, and within strata defined by number of other CV medication classes that are prescribed at randomization (1-4), using blocks of 4 patients to ensure balance within clinics over time. Thus, within each clinic and number of other medication stratum, each set of 4 consecutively enrolled subjects will be randomized to the four study arms. Treatments will be initiated immediately upon randomization, in response to the 7-day gap.
Primary Study Purpose

PREVENTION

Blinding Strategy

NONE

Study Groups

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Usual Care

This group will not receive an intervention. We have included a usual care group to demonstrate the impact of the text messaging interventions above and beyond usual care given that many prior medication adherence interventions have demonstrated small to negligible effects.

Group Type NO_INTERVENTION

No interventions assigned to this group

Generic Nudge

A generic reminder text will be delivered to patients to refill their medication at days 1, 3, 5, 7 and 10 after they been labeled as non-adherent.

Group Type EXPERIMENTAL

Nudge

Intervention Type BEHAVIORAL

Interventions will include a variety of text messages aimed at improving medication adherence.

Optimized nudge

An optimized nudge text will be delivered to patients to remind them to refill their medications at days 1, 3, 5, 7 and 10 after they have been labeled as non-adherent.

Group Type EXPERIMENTAL

Nudge

Intervention Type BEHAVIORAL

Interventions will include a variety of text messages aimed at improving medication adherence.

Optimized nudge plus AI Chat Bot

An optimized nudge text will be delivered to patients to remind them to refill their medications at days 1 and 3 after they have been labeled as non-adherent. If the patient has not filled their medication on days 5 and 7, in addition to receiving an optimized nudge text, an AI will conduct interactive chat via a chat bot to assess barriers filling the medication as described in Aim 1 above. If they still have not filled the medication, they will receive another message on day 10.

Group Type EXPERIMENTAL

Nudge

Intervention Type BEHAVIORAL

Interventions will include a variety of text messages aimed at improving medication adherence.

Interventions

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Nudge

Interventions will include a variety of text messages aimed at improving medication adherence.

Intervention Type BEHAVIORAL

Eligibility Criteria

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Inclusion Criteria

* Patients with the following cardiovascular conditions and respective medication classes:
* Hypertension (Beta-blockers \[B-blockers)\], Calcium Channel Blocker \[CCB\], Angiotensin converting enzyme inhibitors (ACEi), Angiotensin Receptor Blockers \[ARB\], or Thiazide diuretic)
* Hyperlipidemia (HMG CoA reductase inhibitor \[Statins\])
* Diabetes (Alpha-glucosidase inhibitors, Biguanides, DPP-4 inhibitors, Sodium glucose transport inhibitor, Meglitinides, Sulfonylureas, Thiazolidinediones, or statins Coronary artery disease P2Y12 inhibitor \[Clopidogrel, Ticagrelor, Prasugrel, Ticlopidine\], B-blockers, ACEi or ARB or statins)
* Atrial fibrillation (Direct oral anticoagulants, B-blockers, CCB)

Exclusion Criteria

* Patients who do not have a mailing address listed in EHR;
* Patients who do not have a landline or cellphone listed in EHR;
* Currently pregnant if denoted in the EHR at the time of the data pull;
* Patients with a mailing address outside of the state of Colorado;
* Patients that do not speak either English or Spanish.
Minimum Eligible Age

18 Years

Maximum Eligible Age

89 Years

Eligible Sex

ALL

Accepts Healthy Volunteers

Yes

Sponsors

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National Heart, Lung, and Blood Institute (NHLBI)

NIH

Sponsor Role collaborator

University of Colorado, Denver

OTHER

Sponsor Role lead

Responsible Party

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Responsibility Role SPONSOR

Principal Investigators

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Michael Ho, MD, PhD

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Sheana Bull, PhD, MPH

Role: PRINCIPAL_INVESTIGATOR

University of Colorado, Denver

Locations

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UCHealth

Aurora, Colorado, United States

Site Status

University of Colorado Denver

Aurora, Colorado, United States

Site Status

VA Eastern Colorado Health Care System

Aurora, Colorado, United States

Site Status

Denver Health and Hospital Authority

Denver, Colorado, United States

Site Status

Countries

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United States

References

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Jackevicius CA, Li P, Tu JV. Prevalence, predictors, and outcomes of primary nonadherence after acute myocardial infarction. Circulation. 2008 Feb 26;117(8):1028-36. doi: 10.1161/CIRCULATIONAHA.107.706820.

Reference Type BACKGROUND
PMID: 18299512 (View on PubMed)

Ho PM, Spertus JA, Masoudi FA, Reid KJ, Peterson ED, Magid DJ, Krumholz HM, Rumsfeld JS. Impact of medication therapy discontinuation on mortality after myocardial infarction. Arch Intern Med. 2006 Sep 25;166(17):1842-7. doi: 10.1001/archinte.166.17.1842.

Reference Type BACKGROUND
PMID: 17000940 (View on PubMed)

Rasmussen JN, Chong A, Alter DA. Relationship between adherence to evidence-based pharmacotherapy and long-term mortality after acute myocardial infarction. JAMA. 2007 Jan 10;297(2):177-86. doi: 10.1001/jama.297.2.177.

Reference Type BACKGROUND
PMID: 17213401 (View on PubMed)

Spertus JA, Kettelkamp R, Vance C, Decker C, Jones PG, Rumsfeld JS, Messenger JC, Khanal S, Peterson ED, Bach RG, Krumholz HM, Cohen DJ. Prevalence, predictors, and outcomes of premature discontinuation of thienopyridine therapy after drug-eluting stent placement: results from the PREMIER registry. Circulation. 2006 Jun 20;113(24):2803-9. doi: 10.1161/CIRCULATIONAHA.106.618066. Epub 2006 Jun 12.

Reference Type BACKGROUND
PMID: 16769908 (View on PubMed)

Brown MT, Bussell JK. Medication adherence: WHO cares? Mayo Clin Proc. 2011 Apr;86(4):304-14. doi: 10.4065/mcp.2010.0575. Epub 2011 Mar 9.

Reference Type BACKGROUND
PMID: 21389250 (View on PubMed)

Wei L, Wang J, Thompson P, Wong S, Struthers AD, MacDonald TM. Adherence to statin treatment and readmission of patients after myocardial infarction: a six year follow up study. Heart. 2002 Sep;88(3):229-33. doi: 10.1136/heart.88.3.229.

Reference Type BACKGROUND
PMID: 12181210 (View on PubMed)

Wei L, Flynn R, Murray GD, MacDonald TM. Use and adherence to beta-blockers for secondary prevention of myocardial infarction: who is not getting the treatment? Pharmacoepidemiol Drug Saf. 2004 Nov;13(11):761-6. doi: 10.1002/pds.963.

Reference Type BACKGROUND
PMID: 15386713 (View on PubMed)

Lu CY, Ross-Degnan D, Soumerai SB, Pearson SA. Interventions designed to improve the quality and efficiency of medication use in managed care: a critical review of the literature - 2001-2007. BMC Health Serv Res. 2008 Apr 7;8:75. doi: 10.1186/1472-6963-8-75.

Reference Type BACKGROUND
PMID: 18394200 (View on PubMed)

Volpp KG, Loewenstein G, Troxel AB, Doshi J, Price M, Laskin M, Kimmel SE. A test of financial incentives to improve warfarin adherence. BMC Health Serv Res. 2008 Dec 23;8:272. doi: 10.1186/1472-6963-8-272.

Reference Type BACKGROUND
PMID: 19102784 (View on PubMed)

Murray MD, Young J, Hoke S, Tu W, Weiner M, Morrow D, Stroupe KT, Wu J, Clark D, Smith F, Gradus-Pizlo I, Weinberger M, Brater DC. Pharmacist intervention to improve medication adherence in heart failure: a randomized trial. Ann Intern Med. 2007 May 15;146(10):714-25. doi: 10.7326/0003-4819-146-10-200705150-00005.

Reference Type BACKGROUND
PMID: 17502632 (View on PubMed)

Lee JK, Grace KA, Taylor AJ. Effect of a pharmacy care program on medication adherence and persistence, blood pressure, and low-density lipoprotein cholesterol: a randomized controlled trial. JAMA. 2006 Dec 6;296(21):2563-71. doi: 10.1001/jama.296.21.joc60162. Epub 2006 Nov 13.

Reference Type BACKGROUND
PMID: 17101639 (View on PubMed)

Peterson PN, Campagna EJ, Maravi M, Allen LA, Bull S, Steiner JF, Havranek EP, Dickinson LM, Masoudi FA. Acculturation and outcomes among patients with heart failure. Circ Heart Fail. 2012 Mar 1;5(2):160-6. doi: 10.1161/CIRCHEARTFAILURE.111.963561. Epub 2012 Jan 13.

Reference Type BACKGROUND
PMID: 22247483 (View on PubMed)

Gurol-Urganci I, de Jongh T, Vodopivec-Jamsek V, Atun R, Car J. Mobile phone messaging reminders for attendance at healthcare appointments. Cochrane Database Syst Rev. 2013 Dec 5;2013(12):CD007458. doi: 10.1002/14651858.CD007458.pub3.

Reference Type BACKGROUND
PMID: 24310741 (View on PubMed)

de Jongh T, Gurol-Urganci I, Vodopivec-Jamsek V, Car J, Atun R. Mobile phone messaging for facilitating self-management of long-term illnesses. Cochrane Database Syst Rev. 2012 Dec 12;12(12):CD007459. doi: 10.1002/14651858.CD007459.pub2.

Reference Type BACKGROUND
PMID: 23235644 (View on PubMed)

Vodopivec-Jamsek V, de Jongh T, Gurol-Urganci I, Atun R, Car J. Mobile phone messaging for preventive health care. Cochrane Database Syst Rev. 2012 Dec 12;12(12):CD007457. doi: 10.1002/14651858.CD007457.pub2.

Reference Type BACKGROUND
PMID: 23235643 (View on PubMed)

Ho PM, Glorioso TJ, Allen LA, Blankenhorn R, Glasgow RE, Grunwald GK, Khanna A, Magid DJ, Marrs JC, Novins-Montague S, Orlando S, Peterson P, Plomondon ME, Sandy LM, Saseen JJ, Trinkley KE, Vaughn S, Waughtal J, Bull S. Personalized Patient Data and Behavioral Nudges to Improve Adherence to Chronic Cardiovascular Medications: A Randomized Pragmatic Trial. JAMA. 2025 Jan 7;333(1):49-59. doi: 10.1001/jama.2024.21739.

Reference Type DERIVED
PMID: 39621340 (View on PubMed)

Glasgow RE, Knoepke CE, Magid D, Grunwald GK, Glorioso TJ, Waughtal J, Marrs JC, Bull S, Ho PM. The NUDGE trial pragmatic trial to enhance cardiovascular medication adherence: study protocol for a randomized controlled trial. Trials. 2021 Aug 11;22(1):528. doi: 10.1186/s13063-021-05453-9.

Reference Type DERIVED
PMID: 34380527 (View on PubMed)

Luong P, Glorioso TJ, Grunwald GK, Peterson P, Allen LA, Khanna A, Waughtal J, Sandy L, Ho PM, Bull S. Text Message Medication Adherence Reminders Automated and Delivered at Scale Across Two Institutions: Testing the Nudge System: Pilot Study. Circ Cardiovasc Qual Outcomes. 2021 May;14(5):e007015. doi: 10.1161/CIRCOUTCOMES.120.007015. Epub 2021 May 17.

Reference Type DERIVED
PMID: 33993727 (View on PubMed)

Provided Documents

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Document Type: Study Protocol and Statistical Analysis Plan

View Document

Related Links

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Other Identifiers

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UH3HL144163

Identifier Type: NIH

Identifier Source: secondary_id

View Link

18-2779

Identifier Type: -

Identifier Source: org_study_id

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