Clinical Trial Details
— Status: Completed
Administrative data
| NCT number |
NCT01395095 |
| Other study ID # |
MEC-2010-391 |
| Secondary ID |
|
| Status |
Completed |
| Phase |
N/A
|
| First received |
July 14, 2011 |
| Last updated |
March 14, 2016 |
| Start date |
September 2011 |
| Est. completion date |
March 2016 |
Study information
| Verified date |
March 2016 |
| Source |
Erasmus Medical Center |
| Contact |
n/a |
| Is FDA regulated |
No |
| Health authority |
Netherlands: The Central Committee on Research Involving Human Subjects (CCMO) |
| Study type |
Interventional
|
Clinical Trial Summary
The objective is to investigate whether in acute coronary syndrome patients the cardiac risk
profile will improve with 2 new extended cardiac rehabilitation interventions and if these
patients maintain healthier life style habits and a more active life style compared to
patients randomized to standard cardiac rehabilitation.
Description:
Rationale: Throughout the western world, healthy life style management is becoming
increasingly important. Therefore, secondary prevention with an emphasis on lifestyle
adjustments should be the cornerstone of modern cardiac rehabilitation (CR). This study may
demonstrate the benefits of extended CR with respect to achieving optimal long term
secondary prevention goals.
Objective: The objective is to investigate whether in acute coronary syndrome patients the
cardiac risk profile will improve with 2 new extended cardiac rehabilitation interventions
(OPTICARE and COACH) and if these patients maintain healthier life style habits and a more
active life style compared to patients randomized to standard CR.
Study design: The proposed trial is a singlecenter, multi-disciplinary randomized controlled
trial with a 18-month follow-up. In total 900 patients will be randomized into 3 arms:(1)
Standard CR according to the Dutch guidelines; (2) OPTICARE intervention: standard CR and
participation in multifactorial lifestyle sessions during rehabilitation and additional
sessions at 4, 6 and 12 months and a personalized program to promote an active lifestyle;
(3) COACH intervention: standard CR according to the Dutch guidelines followed by 5
telephone delivered coaching sessions starting at 6 weeks intervals (up to 6 months). The
enrollment period will be 24 months, the intervention period is 12 months and the duration
of the follow-up will be another 6 months. Assessments will take place at 4 time points: at
baseline, 12 weeks after inclusion (end standard CR), at 12 and at 18 months.
Study population: Patients referred for standard CR will be included to participate in this
trial. ACS patients treated with primary or elective PCI or CABG, with a stable medical
condition and providing written informed consent are eligible to participate.
Intervention: OPTICARE intervention: Standard CR and obligation to participate in
multifactorial lifestyle and risk factor sessions (medical information, dietary advises,
risk factors and emotional advises). Individual sessions and a personalized home-based
program to promote an active life style upon instruction of a physiotherapist and physical
activity counsellor during and after completion of rehabilitation. If applicable, patients
will participate in smoking cessation, dietary and stress management programs. Additional
supervised multifactorial lifestyle and risk management training sessions of each 2 hours
are provided at 4, 6 and 12 months. COACH intervention: standard CR according to the Dutch
guidelines followed by 5 telephone based coaching sessions starting at 6 weeks intervals up
to 6 months. The coaching sessions include assertiveness training, goal setting and
reassessment.
Main study parameters/endpoints: The main objective is to investigate whether in patients
randomized to extended CR (OPTICARE or COACH) cardiac risk profile will be improved, if
these patients maintain healthier life style habits and do achieve an increase in daily
activity level compared to patients randomized to standard CR.
Statistical Analysis Plan (SAP) of the OPTICARE study
Introduction The proposed trial is a single center, multi-disciplinary open-label randomized
controlled trial. Between October 2011 and August 2014 922 patients were randomized into 3
arms:(1) Standard CR according to the Dutch guidelines (Opticare-Basic) (n=308); (2)
OPTICARE intervention: standard CR with the addition of a personalized program to promote an
active lifestyle. Besides, additional sessions were offered at 4, 6 and 12 months to improve
long-term adherence to lifestyle changes. (Opticare-Capri) (n=310); (3) Heart COACH
intervention: standard CR according to the Dutch guidelines followed by 5-6 telephone
delivered coaching sessions starting one after finishing standard CR at 6 weeks intervals up
to 12 months (Opticare-Achmea Heart Coach) (n=304). The intervention period is 12 months and
the duration of the follow-up will be another 6 months. Assessments will take place at 4
time points: at baseline, 12 weeks after inclusion (end standard CR), at 12 and at 18
months.
Current status The study will be finished in January 2016. During September 2015 and January
2016 the data are checked and cleaned. In February 2016 the database will be closed and the
statistical analyses can start.
Statistical analysis plan for Cardiology Primary end point and sample size Primary end point
is the SCORE risk function measured at 18 months post randomization (Conroy RM et al, Eur HJ
2003; 24:987-1003). This score estimates 10-year risk of fatal cardiovascular disease. The
SCORE risk function includes age, gender, systolic blood pressure, total cholesterol and
smoking behaviour. The RESPONSE trial (Jorstadt HT, Heart 2013; 99:1421-1430) studied the
effectiveness of a nurse-coordinated outpatient risk management program in cardiac patients.
That strategy was associated with a 17 % reduction in SCORE Risk function as compared with
standard care. Based on these data, and taking into account the more intensive interventions
that we will perform, we expect in both the OPTICARE-CAPRI and in the OPTICARECOACH arm at
least a 20 % reduction in the SCORE Risk Score at 1.5 years: from 5.40 to 4.32 points with
an estimated standard deviation (SD) of 4.5. With 274 patients in each treatment arm, the
study has 80 % power (beta-error=0.02) to detect this difference with an alpha-error of 0.05
(2-sided test). We will enroll a total 300 patients in each treatment arm, taking into
account a 10 % drop-out rate.
N.B. In all analyses Opticare-Capri will be compared with Opticare-Basic and Opticare-Heart
Coach with Opticare-Basic. The sample size computation was such that Opticare-Capri will not
be compared with Opticare-Heart Coach.
Primary analysis: intention-to-treat In total, three analyses will be performed to
investigate the consistency of the different analyses and to investigate whether differences
between the methods can be explained.
Although according to the protocol, no comparisons will be made on cardiac events, these
events (mortality, myocardial infarctions, coronary revascularizations and
rehospitalizations for cardiac reasons) will be collected.
To be investigated: is the RISC score normally distributed? If necessary, a (ln-)
transfrmation will be applied.
Analysis 1 (main analysis): SCORE risk function score at 18 months Opticare-Capri vs
Opticare-Basic (student's t-test) and the same for Opticare-Capri vs Opticare-Basic.
Analyse 2:Mixed models will be used. These models takes into account missing data that is
missing at random (Twisk, 2004). This analysis will include all patients with at least one
measurement. All 4 time points will be included in these models (repeated measurements). At
this way we can optimally analyze changes over time.
Analyse 3: Delta score 18 months vs baseline. All patients with a score at baseline and at
18 months will be included.
Secondary analyses: per protocol Patients have to attend at least 75% of the rehabilitation
sessions to be included in the per protocol analysis, this means 18 training sessions.
Besides, patients included in the Opticare-Achmea Heart Coach have to complete at least 3
out of 5 telephonic coaching sessions. Patients in the OPTICARE-Capri arm were invited to 3
active lifestyle intervention sessions and 3 multifactorial lifestyle and cardiovascular
risk factor group intervention sessions. Only those Opticare patients who attended at least
4 of the 6 possible group sessions, will be included in this per-protocol analysis. It will
be evaluated whether these results coincide with the intention-to-treat results.
The same analyses as described under the intention-to-treat analyses will be performed for
the per protocol analysis and results will be compared to results of the intention-to-treat
analyses.
In the intention-to-treat and in the per protocol analyses also the individual risks factors
systolic blood pressure, total cholesterol and smoking behaviour will be analyzed separately
as dependent variables.
Imputation No imputation will be performed on the end point parameters If necessary,
multiple imputation on missing data of the baseline characteristics will be performed.
Statistical analysis plan for Rehabilitation Medicine Primary end point Primary end point is
daily amount of moderate-to-vigorous physical activity (MVPA) measured by Actigraph
(Bluetooth ® Smart wGT3X-BT).
Sample size Expected amount of minutes in (moderate-intensity) daily activity at 18 months
post randomization Opticare-Basic program: 16 minutes/day (SD 13) Based on amount of minutes
at start of rehabilitation(Ref. Oliveira and Stevenson et al) Opticare-Achmea Heart Coach:
25 minutes/day (SD 20) Based on amount of minutes at completion of standard CR (Ref.
Stevenson et al), it is expected that patients in Opticare-Achmea Heart Coach reach (?) this
level of activity Opticare-Capri: 32 minutes/day (SD 23) It is expected that patients in
Opticare-Capri reach the recommended level of physical activity. At 2 year follow-up,
Oliveira et al found that patients were active for a mean of 63.7 minutes at the end of a
counselling session, long term effects are unknown. SD is based on highest SD measured by
Oliveira.
With 202 patients in each treatment arm, the study has a power of 80% (beta-error=0.02) to
detect this difference with an alpha-error of 0.05, taking into account the ANOVA Bonferroni
correction (2-sided test) Taking into account missing values, failure of measurement system
and drop outs (20%), a total of 245 patients in each treatment arm will be enrolled.
Analyses: per protocol Patients that dropped out of the study or CR program did not visit
the center anymore, making it impossible to install the Actigraph device. Therefore, by
design a mix of the intention-to-treat-analysis identical and a per-protocol analysis will
be applied. In the CONSORT diagram this design will be explained in more detail.
Per-protocol analysis:
To be investigated: is MVPA normally distributed? If needed, a (ln-) transformation will be
performed.
Analysis 1: MVPA at 18 months Opticare-Capri vs Opticare COACH vs Opticare-Basic (ANOVA) .
Analysis 2: Mixed models. These models takes into account missing data that is missing at
random (Twisk, 2004).
This analysis will include all patients with at least one measurements. All 4 time points
will be included in these models (repeated measurements). In this way we can optimally
analyze changes over time.
Analysis 3: Delta minutes of MVPA 18 months vs baseline. All patients with a valid
measurement at baseline and at 18 months will be included.
N.B. In the analyses also the minutes of sedentary behavior and the distribution of MVPA and
sedentary behavior will be analyzed separately,
