Clinical trial NCT02313987: Endothelial Function-guided Therapy Compared to Usual Care in Patients With NOCAD
Official title: The Impact of Endothelial Function-guided Therapy Compared to Usual Care on Major Adverse Cardiovascular Events in Patients With Chest Pain and Non-obstructive Coronary Artery Disease
Study type: OBSERVATIONAL
Overall status: WITHDRAWN
Conditions: Coronary Atherosclerosis
Lead sponsor: Itamar-Medical, Israel
Sponsor class: INDUSTRY
First posted: 2014-12-10
Enrollment: 0
Sex: ALL
Minimum age (years): 20
Maximum age (years): 79
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Observational model: CASE_CONTROL
Time perspective: PROSPECTIVE
Sampling method: PROBABILITY_SAMPLE
Study population: Subjects with chest pain and non-obstructive coronary artery disease (20-70% diameter luminal narrowing) will be enrolled in the study 2-30 days following the coronary angiograms

Brief summary: The current study is designed to test the hypothesis that compared to conventional treatment; endothelial function-guided treatment reduces adverse cardiovascular events in patients with non-obstructive coronary artery disease documented at clinically indicated coronary angiography.

Detailed description: Subjects with chest pain and non-obstructive coronary artery disease (20-70% luminal diameter narrowing) documented by coronary angiograms will be enrolled in the study 2 - 30 days following the coronary angiograms. Only subjects who have signed an Informed Consent Form and meet all of the eligibility criteria will be qualified for enrollment.

Following the baseline EndoPAT testing subjects will be divided into two groups by their EndoPAT (EndoScore) results:

1. Group A - normal EndoScore: Logarithmic value of RHI (Ln_RHI) \>0.7
2. Group B - abnormal EndoScore: Ln_RHI ≤ 0.7 The subjects of Group B will be randomized in 1:1 ratio (by envelopes with randomization numbers at each site) to Group B1 who will be treated conventionally i.e., "usual care" by the site study team; and Group B2 who will be treated with "enhanced care".

Staff prescribing treatment regime for subjects in group A and B1 ("usual care") along with the subjects in these groups, will be blinded to the EndoScore value.

Subjects of all groups will return for 4 follow-up visits: 180±14days, 360±14days, 720±14days and 1080±14days (study end).

Eligibility criteria: Inclusion Criteria:

* Subjects with chest pain and non-obstructive coronary artery disease documented by coronary angiography with 20-70% luminal diameter stenosis that does not justify coronary revascularization
* Stable subjects without evidence of prior MI/CABG/PTCA.
* Age 20 to 79 years
* Ability to understand the study procedures and provide written informed consent
* Willingness and ability to comply with the study and its scheduled visits and study procedures

Exclusion Criteria:

* Age below 20 over 79 years
* Subjects with documented MI, PTCA or CABG
* Unstable angina
* Any lesion \> 20% luminal narrowing in the left main coronary artery
* Congestive heart failure, NYHA class II - IV
* Severe renal dysfunction, defined as an estimated glomerular filtration rate (eGFR calculated by MDRD) \< 20 mL/min/1.73m2 at screening
* Uncontrolled hyperthyroidism or hypothyroidism as defined by thyroid stimulating hormone (TSH) , 1.0 time the lower limit of normal (LLN) or \> 1.5 times the upper limit of normal (ULN), respectively, at screening
* Symptomatic peripheral artery disease
* History of drug or alcohol abuse
* Active liver disease or hepatic dysfunction, defined as aspartate aminotransferase (AST) or alanine aminotransferase (ALT) 2 times the ULN as determined by local laboratory analysis at screening
* Prior CVA or TIA
* Malignancy (except non-melanoma skin cancers, cervical in-situ carcinoma, breast ductal carcinoma in situ or stage 1 prostate carcinoma) with life expectancy of \< 3 years
* Any planned surgery within 3 months after randomization
* Recipient of any major organ transplant (e.g., heart, lung, liver, bone marrow)
* Severe, concomitant non-cardiovascular disease that is expected to reduce life expectancy to less than 3 years
* Known, concerning active infection or major hematologic, renal, metabolic, gastrointestinal or endocrine dysfunction in the judgment of the investigator
* Currently enrolled in another investigational device or drug study, or less than 30 days since ending another investigational device or drug study(s), or receiving other investigational agent(s). Special clearance can be obtained from the Steering Committee for subjects enrolled in studies not conflicting with this protocol
* History or evidence of any other clinically significant disorder, condition or disease other than those outlined above that, in the opinion of the investigator may compromise the ability of the subject to give written informed consent, would pose a risk to the subject safety, or interfere with the study evaluation, procedures or completion
* Deformities of the digits of the upper extremities, which preclude adequate signal acquisition
* Subjects under the effect of short-acting NTG (3 hours washout period)
* Patient suffering from a medical condition prohibiting blood flow occlusion in both arms

Primary outcomes:
measure: MACE
timeFrame: 3 years
Secondary outcomes:
measure: Rehospitalization for chest pain
timeFrame: 3 years
measure: quality of life questionnaire
timeFrame: 3years
measure: time to the first occurrence of cardiovascular death
timeFrame: 3 years
measure: myocardial infarction
timeFrame: 3 years
measure: Stroke
timeFrame: 3 years
measure: time to the first occurrence of death from any cause
timeFrame: 3 years
measure: hospitalization for worsening heart failure
timeFrame: 3 years
measure: time to the first occurrence of ischemic fatal or non-fatal stroke or transient ischemic attack.
timeFrame: 3 years
Other outcomes:
Locations:
city: Kfar Saba
country: Israel
facility: Meir Hospital
city: Ramat Gan
country: Israel
facility: Tel Hashomer
Study officials:
affiliation: Mayo Clinic
name: Amir Lerman, M.D; Prof
role: PRINCIPAL_INVESTIGATOR
References: