- to reduce the prevalence of Heart Failure (HF) in cancer survivors- to improve screening strategies for early diagnosis of anthracycline-induced cardiotoxicity (AIC)Also the following objectives:- to identify early cardiotoxicity markers- to…
ID
Source
Brief title
Condition
- Lymphomas non-Hodgkin's unspecified histology
- Lymphomas non-Hodgkin's unspecified histology
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
Absolute change in LVEF (between baseline and any follow-up CMRs, whichever
shows worse LVEF).
Secondary outcome
Rate of anthracycline-induced cardiotoxicity events (based on drop in LVEF
between baseline and any CMR of the 2 follow-up CMRs, whichever shows lower
LVEF).
Cardiotoxicity event is defined as one of the following:
- Drop in LVEF between study CMRs of >=10 absolute points regardless the
absolute value of follow- up ejection fraction (EF).
- Drop in LVEF between study CMRs of >=5 to <10 absolute points with a
follow-up EF value <50%
Rate of atrial fibrillation.
Rate of hospital admission for sustained ventricular tachycardia, ventricular
fibrillation (VT/VF) or resuscitated cardiac arrest.
Time to all cause death
Time to HF hospitalization
Rate of tumour regression.
Change in Quality of Life (QOL, scores in questionnaires) between baseline and
2 time-points (after 3rd chemotherapy cycle, and 9 weeks after the last
chemotherapy cycle).
.
Background summary
See page 13-16 of the studyprotocol:
Very recent data show that >35% of patients receiving anthracyclines develop
any form of cardiotoxicity. More importantly, 6% of all patients receiving
anthracyclines (200.000 patients every year in Europe) develop moderate to
severe cardiotoxicity.
There is an unmet need to identify therapies for cancer patients undergoing
anthracycline regimes that can reduce the burden of chronic HF in this
vulnerable population.
Remote ischemic conditioning is a safe and cheap intervention that has been
shown to prevent anthracycline-induced cardiotoxicity in a preclinical model.
Remote ischemic pre-conditioning (RIC) is a phenomenon by which brief,
reversible episodes of ischemia followed by reperfusion in one organ (e.g. an
arm) render remote tissues and organs resistant to injury.
RIC is safe and effective, non-invasive, easily feasible, and inexpensive
intervention, which has been mainly tested in the context of myocardial
infarction and stroke.
Recent evidence suggests that, to be protective, RIC has to be initiated before
the index insult. This is thus the ideal setting for AIC since the chemotherapy
is a planned procedure.
NHL is one of the most common cancer types in Europe, with 115,000 new cases
diagnosed every year, and it is predicted that these figures will rise in the
close future. Most NHL cases require a combination chemotherapy including
anthracyclines.
Study objective
- to reduce the prevalence of Heart Failure (HF) in cancer survivors
- to improve screening strategies for early diagnosis of anthracycline-induced
cardiotoxicity (AIC)
Also the following objectives:
- to identify early cardiotoxicity markers
- to validate a novel ultrafast CMR sequence
Study design
- study phase: phase II
- study type: interventional
- double-blinded, sham-controlled, randomized clinical trial
- primary purpose: to evaluate the efficacy and safety of Remote Ischaemic
Conditioning (RIC) and validation of the novel ultrafast CMR sequence
- Number of Arms: 2
- Randomization (1:1) will be stratified by LVEF on baseline CMR (as quantified
by CMR core lab /CNIC), by research Centre and by patient*s gender.
Patients enrolled undergo baseline Cardiac Magnetic Resonance (CMR), and high
sensitivity troponin (hsTn) and NT-proBNP blood test.
Patients with confirmed LVEF >40% by CMR will be randomized 1:1 to RIC vs
simulated RIC (Sham).
After the 3rd chemotherapy cycle, a second CMR+ hsTn/ NT- proBNP will be
performed for the validation of the early marker of cardiotoxicity.
A third hsTn/ NT-proBNP blood test will be performed in the last chemotherapy
cycle.
9 weeks after finishing chemotherapy, the last CMR+ hsTn/ NT-proBNP will be
performed.
Patients will be followed-up for clinical events at 6, 12, 18, 30 and 42 months
until the last patient undergoes the final CMR.
When the last patient undergoes the last CMR, the follow-up will be closed.
The median follow-up estimation for clinical endpoints is 24 months (range: 6
to 42 months).
Recruitment period: 36 months.
Minimum follow-up of all patients: 9 weeks after the last chemotherapy cycle
(approx. 6 months after recruitment)
Maximum follow-up: 36 months after the last chemotherapy cycle.
Intervention
Intervention is RIC vs simulated RIC (Sham)
The procedure will be performed by using an electric auto-control device for
remote ischemic conditioning (RIC) or simulated RIC (Sham) in the upper limb.
Patients will undergo a RIC/Sham session at home every week during the entire
duration of chemotherapy (last session one week after the last chemotherapy
cycle).
The first RIC/Sham session will be performed at the hospital immediately before
the first chemotherapy cycle.
In addition to weekly home session, each time the patient comes to receive
chemotherapy, a RIC/Sham session will be performed in the hospital immediately
before starting the cycle.
If the same day of weekly home therapy coincides with the chemotherapy cycle,
the home session will not be performed.
In all other cases, the week they receive the chemotherapy cycle, the patient
will undergo 2 sessions of RIC/Sham (at home as scheduled plus the day of the
chemotherapy cycle).
Study burden and risks
- The RIC/Sham technique is a safe and well-tolerated procedure,but it may
be associated with some mild-moderate harmful events like: tingling,
redness of skin, pins and needles, skin marking, pain, uncomfortable,
numbness, tightness and swelling fingers or hand, loss of sensitivity or
inability to move the upper arm, forearm, and/or hand, wrist drop or
deficiency to extend the wrist, petechiae or hematoma.
- Quality of life is part of this trial. This could be experienced as a
burden.
- There may be some discomfort from the measurements during the study,:
- collection of blood: the subject may experience bruising or
irritation at the site where the needle enters the skin. Some patients may
faint and, in
rare cases, get an infection.
- CMR scan: There are no known risks or side effects of a CMR scan. If
a contrast agent is used, the investigator will inform the subject of
possible side effects or an allergic reaction.
- ECG (electrocardiogram): There is usually no risk associated with
undergoing an ecg. The stickers may pull on the subject's skin or cause
redness or itching.
- Participating in the study will cost extra time
- Patients have to comply with the study agreements.
Melchor Fernández Almagro 3
Madrid 28029
ES
Melchor Fernández Almagro 3
Madrid 28029
ES
Listed location countries
Age
Inclusion criteria
- >=18 years old
- First NHL diagnosis
- Scheduled to undergo >=5 chemotherapy cycles including anthracyclines
.Pre-chemo LVEF >40% on screening echocardiography.
- Presence of >=1 of the following risk factors for developing cardiotoxicity:
o Previous coronary artery disease without evidence of prior myocardial
infarction (any of the following):
* Previous coronary revascularisation (PCI or CABG)
* Medical history of previous significant non-revascularized coronary stenosis
o LVEF 41-54%
o Age >= 65 years old
o Previous diagnosis of arterial hypertension (with or without treatment)
o Chronic kidney disease (estimated glomerular filtration rate <
60ml/min/1.73m2)
o Current or former smoker.
o Obesity (BMI>=30 kg/m2)
o LVH on screening echocardiography (LV thickness >=12mm).
o High alcohol intake (>=21 alcoholic beverages per week)
- Sinus rhythm on screening ECG
Exclusion criteria
- History of any of the following diseases:
o Any cancer who received anthracyclines treatment before the index episode
o Previous clinical diagnosis of heart failure.
o Previous diagnosis of acute myocardial infarction.
o Permanent atrial fibrillation (AF).
o Severe valvular or sub-valvular heart disease, either as a previously
clinical diagnosis or as a finding on screening echocardiography.
o Severe peripheral arterial disease in the upper extremities or arteriovenous
(AV) shunt in the arm selected for RIC.
- Clinical diagnosis of diabetes, with or without treatment.
- Contraindication for contrast enhanced CMR
- Severe thrombocytopenia (platelet <50) on any blood test within the previous
3 months.
- Patients participating in other randomized clinical trials.
- Impossibility to consent or undergo study follow-ups
Design
Recruitment
Medical products/devices used
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL83331.000.23 |