Clinical Trial Details
— Status: Recruiting
Administrative data
| NCT number |
NCT05637853 |
| Other study ID # |
TELE-FASTER-HF |
| Secondary ID |
|
| Status |
Recruiting |
| Phase |
|
| First received |
|
| Last updated |
|
| Start date |
October 22, 2022 |
| Est. completion date |
October 22, 2024 |
Study information
| Verified date |
November 2022 |
| Source |
Göteborg University |
| Contact |
Tomas Mellberg, MD, PhD |
| Phone |
+46313421000 |
| Email |
tomas.mellberg[@]vgregion.se |
| Is FDA regulated |
No |
| Health authority |
|
| Study type |
Observational [Patient Registry]
|
Clinical Trial Summary
Research hypothesis:
Fast telemonitored medical sequencing in patients with heart failure with reduced ejection
fraction (HFrEF) is safe and feasible.
Background:
Modern therapy for HFrEF offers a highly effective arsenal of drugs, devices and
interventional therapies, yet mortality and morbidity remain high in the cohort. One major
problem is that drug therapy introduction and up titration has been very hard to implement in
a majority of HFrEF patients. Most previous telemonitoring studies have focused on the
continuous monitoring of patients and the monitoring itself has been the main intervention. A
potentially more effective way to use telemonitoring in heart failure patients may be to
combine the technique with a medical intervention when the patients are most vulnerable to
heart failure events. The best therapeutic window lies in the period after newly diagnosed
heart failure or right after a recent hospitalization following worsened chronic HFrEF.
Method:
We aim to use telemonitoring for fast sequencing of heart failure drugs for patients with
HFrEF.
Description:
Our hospital and other centra in "Västra Götalandsregionen" has been exploring telemonitoring
in a pilot study that started in 2019 and included 100 patients. This study has used an
application from Telia called Telia Health Monitoring (THM). Through this application
patients may report both objective parameters such as weight, pulse, blood pressure as well
as subjective information for example estimation of symptoms and well-being. Overall, this
pilot study has reported good safety data and patient satisfaction. In the present study, we
intend to use the same application and health care infrastructure as in the pilot study.
Study synopsis
1. Primary aim:
The primary aim is to assess the safety and feasibility of fast telemonitored sequencing
of heart failure medications in HFrEF patients.
2. Study population:
Patients (inpatient or outpatient) with confirmed HFrEF who are either newly diagnosed
(within 3 month) or hospitalized for worsening heart failure (within 1 month) and in
need of medical sequencing are eligible. Different hospitals within "Västra
Götalandsregionen" will participate. Participating centres are Sahlgrenska University
hospital/Sahlgrenska, Sahlgrenska University hospital/Östra and Skaraborg Hospital
Skövde. The aim is also to recruit Södra Älvsborgs hospital as a centre since all these
clinics except for Sahlgrenska University hospital/Sahlgrenska have previous experience
of the home monitoring equipment.
3. Objectives:
i. Primary objective To study whether fast telemonitored sequencing in HFrEF patients is
safe and feasible.
ii. Secondary objectives To investigate whether titration to full target doses of all
four classes of HFrEF medications is achievable within 8 weeks of telemonitored
sequencing.
To investigate whether fast telemonitored sequencing in patients with HFrEF results in
earlier OMT compared to prescription patterns from Riks-Svikt (Swedish Heart Failure
registry-Swede-heart failure).
To investigate the proportion of patients still on OMT after 1-, 3- and 5-years
follow-up compared to prescription patterns from Riks-Svikt.
To investigate if objective signs are observed from telemonitored values in patients
non-compliant to the fast titration scheme.
Prediction models to identify patients tolerating rapid HF medication titration.
In depth analyses of health assessment questionnaires evaluating the patients
experiences of home monitoring.
4. Study design:
This is an observational prospective study. All HFrEF patients eligible for study
inclusion will be asked to participate in the telemonitored fast medical sequencing
intervention. Patients who do not wish to be included in the intervention arm are going
to be followed and titrated according to standard of care, in line with local heart
failure treatment guidelines. This approach involves visits to the heart failure
outpatient clinic with gradual titration of HFrEF medication.
5. Method:
The study population in TELE-FASTER-HF is patients with newly diagnosed HFrEF (within
three months) or patients who are hospitalized for worsening heart failure (within 1
month) and in need of titration of HFrEF medications. The patients will be screened for
eligibility for the study at a first nurse visit at the heart failure out-patient clinic
or before discharge from the hospital. Eligible patients need to have access to a
smartphone and internet connection at home. In total, 200 patients are going to be
equipped with a telemonitoring equipment. The application from Telia also holds a health
assessment questionnaire that can be sent to the out-patient clinic. Blood pressure,
pulse and weight are reported daily to a designated heart failure nurse. Every week the
patient will be automatically asked to answer the health assessment questionnaire which
will be sent to the clinic. All parameters will have specified cut-off values for
alerting the designated nurse to take action if needed following standard clinical
procedures used by the heart failure nurses. Blood samples will be collected at
screening visit and during several steps of medical sequencing in accordance with
standard procedures. The purpose is to achieve full titration of all four classes of
HFrEF medication within 8 weeks after newly diagnosed heart failure or acute
decompensation of chronic heart failure. Each patient will be home monitored for a
period of 6 mounts.
6. Medical sequencing:
Sequencing will be initiated and carried out in a standardized format for all patients
included in the intervention arm. All patients will be started on an SGLT2i and a betablocker
right after study inclusion. In the second week, RAASi will be introduced with either
angiotensin converting enzyme inhibitor (ACEi) or angiotensin receptor neprilisyn inhibitor
(ARNI). If the patient is intolerant to either of these, an angiotensin receptor blocker
(ARB) will be introduced. During the following weeks, both BB and ACEi/ARNI/ARB will be up
titrated every second week according to the sequencing algoritm, figure 2. MRA will be
introduced and up titrated in week 3 and 7 respectively. If the patient is already on either
BB or ACEi/ARNI/ARB/MRA they will continue with the previous prescription and dose until the
titration scheme indicates up titration.
Eligibility criteria
1. Inclusion criteria:
Patients diagnosed with HFrEF and without contraindications for either of the following
drug classes: SGLT2i, BB, RAASi and MRA.
2. Exclusion criteria:
Estimated glomerular filtration rate (eGFR)<45 ml/min Patients with HFrEF already on
treatment with either BB or ACEi/ARNI/ARB and up titrated to >50% of maximal recommended
dose.
Patients who do not have access to a smartphone or internet connection at home. Patients not
able to comprehend the technical aspects of home monitoring or unable to give informed
consent.
Endpoints:
Primary endpoint Safety and feasibility of fast telemonitored sequencing of heart failure
medications in HFrEF patients.
Predefined safety endpoint: incidence of treatment-emergent adverse events up to 180 days
from start of sequencing. Changes in vital signs compared to base-line will be recorded.
Clinical decision will be based on ESC guidelines for heart failure 2021.
Secondary endpoints:
1. Proportion of patients reaching full doses of BB, SGLT2i, RAASi and MRA within 8 weeks
of medical sequencing with home monitoring
2. Proportion of patients capable of reaching full doses of BB, SGLT2i, RAASi and MRA
compared to reported prescriptions from Riks-Svikt.
3. Proportion of patients still on OMT after 1-, 3- and 5-years follow-up compared to
prescription patterns from Riks-Svikt.
4. Prediction models to identify patients tolerating rapid HF medication titration.
5. In depth analyses of reported vital signs and their relation to prescription
interruption.
6. In depth analyses of health assessment questionnaires evaluating patients experiences of
home monitoring.
Statistical considerations:
The number of patients in the intervention group was estimated from a power calculation based
on a theoretical study design where patients were randomization between conventional
follow-up and telemonitoring and fast titration with 1:1 allocation. With an 85% power at a
significance level of alfa= 0.005 to show a 50% difference in improvement in reaching OMT in
the intervention group compared with standard of care a sample size of 200 patients in each
treatment arm is needed.
Patients with home monitoring will be compared with a control group from Riks-Svikt. The
patients will be matched 1:10 for age, gender and heart failure diagnose with controls from
Riks-Svikt.
All analyses will be performed with the statistical software R (R v3.5.2; R Foundation for
Statistical Computing, Vienna, Austria). Nominal significance levels will be 0.05 and all
test performed will be two-sided, when appropriate. All confidence intervals will be 95%.
Safety and feasibility endpoints will mainly be presented with descriptive statistics. For
descriptive baseline characteristics, categorical data are presented as numbers and
percentages and continuous data as means with standard deviation or medians with
interquartile range. Cox proportional hazard models will be used to calculate the differences
between intervention and control groups in reaching OMT, yielding hazard ratios (HR) with 95%
CI.
Ethical consideration:
The study will be conducted in compliance with the ICH Good Clinical Practice Guidelines and
in accordance with the ethical principles of the Declaration of Helsinki.
The investigators will ensure that all participants will be given full and adequate oral and
written information about the nature, purpose, possible risk and benefit of the study and
ensure that all subjects are notified that they are free to discontinue with the study at any
time. Signed and dated informed consent will be obtained before conducting any study specific
procedure and stored in the Study Master File. A copy of the signed Informed Consent Form
will also be given to each participant.
Scientific importance:
The scientific evidence regarding modern heart failure treatment is substantial and there is
no doubt regarding these drugs powerful potential in reducing morbidity and improving
prognosis in patients with HFrEF. This group of patients is large and the number of patients
in need for treatment is increasing. Even so, a large proportion of these patients are not
prescribed these drugs and if they are, they do not reach target doses in reasonable time. In
fact, a majority of HFrEF patients never reach target doses of heart failure drugs.
This study addresses several unexplored parts of heart failure drug therapy introduction and
sequencing. Since there are no previous studies addressing implementation of the latest
guidelines for HFrEF drugs using home monitoring, this study has the potential of filling an
important scientific gap as well as making a large impact in streamlining therapy for these
patients.
Risk/benefit assessment:
This is not an experimental drug intervention. All the drugs used in treatment for HFrEF have
been safely used in up titration in several previous studies. The concept of home monitoring
in heart failure has been used in previous different trials and has shown to be safe. The
patients will be remotely monitored daily by heart failure nurses, in this manner patients
will be observed more often than in clinical routine which one could argue even may increases
the safety for patients when prescribing heart failure drugs. Furthermore, patients will also
be followed by blood sampling repeatedly to avoid any adverse drugs events.
Data storage and management:
Study data will be collected using CRFs. The reason for any excluded data or protocol
deviations will be documented in the study report. CRF documentation, study documents and
other source data will be retained for at least 10 years after finalization of the study.
Information about the patient involved in the current study, the consent date, name of the
study must be recorded, saved and stored according to national regulations in the hospitals
electronic medical records (Melior).
All patients will receive a unique study code and the study code list will be kept separately
from all other data to assure patient confidentiality. Data analyses will be performed on
anonymous data set and study results will be presented on a population level with no
possibility to identify unique individual. The results will be presented in scientific
peer-reviewed journals.
