IMproving reModeling in Acute myoCardial Infarction Using Live and Asynchronous TElemedicine. (IMMACULATE)

The proposed research aims to compare Left ventricular remodeling outcomes among patients with AMI and elevated NT-pro-B-type natriuretic peptide receiving telemedicine-guided post-MI treatment vs. non-telemedicine guided treatment.

Study Overview

• Status: Unknown
• Conditions: Medication Adherence; Acute Coronary Syndrome; Left Ventricular Remodeling
• Intervention / Treatment: Other: Telemedicine

Detailed Description

Acute Myocardial Infarction (AMI) accounts for more than 6,000 admissions to Singapore hospitals each year. Contemporary treatment, including percutaneous intervention (angioplasty and stenting) and adjunctive drug therapy, has reduced early mortality from AMI.

In many healthcare systems, Hospital scorecards stipulate prescription of appropriate drugs upon discharge after hospitalization for AMI. These drugs include aspirin, a platelet P2Y12 inhibitor, angiotensin converting enzyme inhibitors (ACE-I) or angiotensin receptor blockers (ARB), beta-blockers and lipid-lowering drugs. Such quality improvement programs have led to an increase in prescription of these drugs upon discharge. Yet, 2 problems remain pervasive:

1. dose optimization; how the investigators escalate patients to the most effective drug doses, and
2. drug adherence; whether patients are taking these drugs regularly.

These 2 problems stem largely from the traditional model of episodic care entailing face-to-face visits between patient and healthcare practitioner. Inadequate dose optimization is most relevant to ACE-I/ARB and beta-blockers as healthcare practitioners necessarily prescribe low doses of these drugs at discharge to avoid excessive lowering of blood pressure soon after an AMI. Yet, these drugs are most effective at preventing adverse ventricular remodeling when patients take them at their maximum tolerated doses. In clinical trials, titrating these ACE-I/ARB and beta-blockers to target doses has required weekly outpatient visits, a model of care that most healthcare systems cannot afford.

The investigators hypothesize that a telemedicine-based system of care will lead to a greater reduction in ventricular remodeling as compared with usual care, by improving dose optimization and adherence to ACE-I/ARB and beta-blockers in patients with recent AMI.

Participants with AMI (n=300) will be recruited during the index hospitalization. A key inclusion criteria is an elevated NT-proBNP measurement during the index hospitalization. Participants will first undergo stratified randomization according to ST-segment classification (STEMI/NSTEMI), thereafter randomized into the Telehealth versus Control group in 1:1 sequential block randomization (blocks of 4 and 6). The telehealth intervention group will have their blood pressure and heart rate monitored twice daily at home for 2 months, with alternating titration between ACE-inhibitors and betablockers weekly during the first 2 months. After 2 months, they will continue on telemedicine consultation for 4 months; coaching on drug adherence, drug side-effects management and monitoring of symptoms. A smartphone-based app developed by PEACH Intellihealth will provide structured health education, medication reminders and real-time text messaging with telehealth professionals.

All participants enrolled will be put on 1 year of dual antiplatelet therapy, have a cardiac MRI done both at baseline and 6-months, and followed up with cardiologist review visit at 1, 6 and 12 months. Major adverse cardiovascular and cerebrovascular events will be assessed during each cardiologist review visit, and beyond 12 months, it will be assessed by either phone calls or online/mailed questionnaires at 18 and 24 months.

Four substudies have been planned: a substudy to assess the impact of telemedicine on readmissions (ALTRA), a substudy to assess the effect of telemedicine on adherence to antiplatelet therapy (TICA), a substudy to assess the cost-effectiveness of telemedicine (CEA) and a substudy to assess the effect of telemedicine on MR-PET measured cardiac work efficiency (CES).

• Study Type: Interventional
• Enrollment (Anticipated): 300
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Singapore
  • Singapore, Singapore, 308433
    • Recruiting
    • Tan Tock Seng Hospital
    • Contact: Tasha Mahadi; Phone Number: +65 63578124; Email: tashama@ttsh.com.sg
    • Principal Investigator: Hee Hwa Ho
    • Sub-Investigator: Yeong Shyan Lee
    • Sub-Investigator: Prabath F Joseph
  • Singapore, Singapore, 119228
    • Recruiting
    • National University Heart Centre Singapore
    • Contact: Sock Cheng Poh; Phone Number: +65 66015951; Email: sock_cheng_poh@nuhs.edu.sg
    • Contact: Karen Koh; Phone Number: +65 67726884
    • Principal Investigator: Mark Chan
  • National Heart Research Institute
    • Singapore, National Heart Research Institute, Singapore, 169609
      • Recruiting
      • National Heart Centre Singapore
      • Contact: Derek Hausenloy; Phone Number: +65 65166719; Email: d.hausenloy@ucl.ac.uk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 21 years to 85 years (Adult, Older Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion criteria

1. Clinically diagnosed STEMI or NSTEMI* within the last 7 days at high risk of ventricular remodeling

   • Typical history of ischemic chest pain or angina equivalent symptoms (e.g. acute onset dyspnea)
   • Typical rise or fall of cardiac enzymes with at least one value of cardiac troponin I≥10 ug/L.
   • ECG changes required for diagnosis of STEMI: ≥0.1mV ST segment elevation in two or more contiguous limb leads or precordial leads or presence of Q waves ≥0.02 sec in two or more contiguous limb leads or precordial leads, or new onset left bundle branch block (LBBB), *The definition of STEMI and NSTEMI follows the 3rd universal definition of MI [19]
2. Pre-discharge NTproBNP ≥300 pg/mL for both STEMI and NSTEMI
3. Undergone PCI for the index event
4. Age >21 years and <85 years

Exclusion criteria

1. Hypersensitivity to ticagrelor, aspirin or any excipients
2. Active pathological bleeding
3. History of intracranial haemorrhage
4. Bacterial Infection within 6 weeks preceding the primary angioplasty, HIV, autoimmune disease (e.g. SLE, rheumatoid arthritis, scleroderma and Grave's disease, etc) or on immunosuppressive therapy
5. Women of child-bearing potential, known to be pregnant, breast-feeding, or intend to become pregnant during the study period
6. Malignancy within last 2 years
7. History of significant valvular heart disease (moderate or severe MS, MR, AS, AR, TR)
8. Planned CABG within the next 6 weeks
9. Unable to be weaned off inotropes or IABP
10. Active asthma or any other contraindications to beta-blockers
11. Arrhythmias precluding proper CMR image acquisition, such as atrial fibrillation and frequent atrial or ventricular ectopy of > 1 in 5 intrinsic QRS complexes
12. Contraindications to cardiac magnetic resonance imaging including claustrophobia, pacemaker or ICD implantation, mechanical valve or other metallic implants
13. Severe liver impairment due to chronic liver disease e.g. advanced alcoholic liver cirrhosis or primary biliary cirrhosis
14. Significant renal impairment (eGFR <50ml min-1), end stage renal failure on renal replacement therapy
15. Anaemia (Hb<10 g/dL).
16. Psychosocial barriers to telemedicine adoption (screening for education level, dementia, substance abuse and other psychological disorders)
17. Participants who cannot be followed up
18. Participants not able or willing to consent for study.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Health Services Research
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Telemedicine; The telehealth group will be remotely monitored and managed on medication adherence, dosage titration, and management of drug side effects, through a combination of feed-forward blood pressure monitoring, app-based education and medication reminders, and remote consultations.	Other: Telemedicine; Participants enrolled will be randomised 1:1 to either telemedicine arm or standard care arm.
No Intervention: Standard care; The standard care group will receive face-to-face consultations at one month, 6 months and 12 months.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Difference in Left Ventricular End-Systolic Volume (ml)	Difference in Left Ventricular End-Systolic Volume (ml) measured on cardiac magnetic resonance imaging	6 months

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Haemodynamic Stress	Frequency of participants with reduction in NT-proBNP <20%	6 months
Infarct size (grams and % of total LV mass)	Infarct size (grams and % of total LV mass) measured on cardiac magnetic resonance imaging	6 months
Adenosine diphosphate-induced platelet reactivity	Difference in Multiplate ADP test (AU*min)	6 months
Hospitalisation & readmission	Difference in incidence of Death, MI, Stroke, readmission for recurrent ischaemia requiring unplanned revascularization and readmission for heart failure.	2 years

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Quality of Life	Difference in QoL outcome measures	2 years
Medication Adherence	Difference in medication adherence score and pill count	12 months

Collaborators and Investigators

• Sponsor: National University Heart Centre, Singapore
• Collaborators: National University Hospital, Singapore; Tan Tock Seng Hospital; National University, Singapore
• Investigators: Study Chair: A. Mark Richards, National University Heart Centre, Singapore

Publications and helpful links

General Publications

• Arnold SV, Spertus JA, Masoudi FA, Daugherty SL, Maddox TM, Li Y, Dodson JA, Chan PS. Beyond medication prescription as performance measures: optimal secondary prevention medication dosing after acute myocardial infarction. J Am Coll Cardiol. 2013 Nov 5;62(19):1791-801. doi: 10.1016/j.jacc.2013.04.102. Epub 2013 Aug 21. Erratum In: J Am Coll Cardiol. 2014 Mar 11;63(9):944.
• Chan MY, Koh KWL, Poh SC, Marchesseau S, Singh D, Han Y, Ng F, Lim E, Prabath JF, Lee CH, Sim HW, Chen R, Carvalho L, Tan SH, Loh JPY, Tan JWC, Kuwelker K, Amanullah RM, Chin CT, Yip JWL, Lee CY, Gan J, Lo CY, Ho HH, Hausenloy DJ, Tai BC, Richards AM; IMMACULATE Investigators. Remote Postdischarge Treatment of Patients With Acute Myocardial Infarction by Allied Health Care Practitioners vs Standard Care: The IMMACULATE Randomized Clinical Trial. JAMA Cardiol. 2021 Jul 1;6(7):830-835. doi: 10.1001/jamacardio.2020.6721.

Study record dates

Study Major Dates

• Study Start (Actual): June 1, 2015
• Primary Completion (Anticipated): December 1, 2019
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: June 7, 2015
• First Submitted That Met QC Criteria: June 7, 2015
• First Posted (Estimate): June 10, 2015

Study Record Updates

• Last Update Posted (Actual): March 29, 2018
• Last Update Submitted That Met QC Criteria: March 28, 2018
• Last Verified: March 1, 2018

More Information

Terms related to this study

• Keywords: Acute Myocardial Infarction; Telemedicine; Readmissions
• Additional Relevant MeSH Terms: Ischemia; Pathologic Processes; Necrosis; Myocardial Ischemia; Heart Diseases; Cardiovascular Diseases; Vascular Diseases; Pathological Conditions, Anatomical; Myocardial Infarction; Infarction; Acute Coronary Syndrome; Ventricular Remodeling
• Other Study ID Numbers: 2014/00793

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No