Plain English Summary
Background and study aims
Coronary heart disease (CHD), also known as ischemic heart disease, is one of the leading causes of death worldwide. CHD develops because of the build-up of fatty deposits (plaque) on the walls of the coronary arteries (the arteries that supply the heart with oxygen-rich blood). When arteries are blocked or narrowed, the heart does not receive enough blood to function properly, which can cause pain and tightness in the chest (angina), or even lead to a heart attack. There are several types of angina, the most common being stable angina (where the pain is brought on by an obvious trigger, such as exercising). An angioplasty is a common procedure in which a thin tube (catheter) is placed in the narrowed blood vessel. A small balloon on the tip of the catheter is gradually inflated to reopen the artery and flatten the blockage against the artery wall. A mesh-like tube (stent) is often placed inside the artery to keep it open (percutaneous coronary intervention). In about 5-10% of patients, the part of the artery that was reopened in the angioplasty can become narrowed again (restenosis). Nitrate is a chemical which plays an important part in regulating blood pressure and blood flow. It is commonly found in green leady vegetables and beetroot. Recent studies have shown that including nitrate in the diet could help to prevent or reduce restenosis. The aim of this study is to find out whether drinking nitrate-rich beetroot juice can help to prevent restenosis in patients who have had a percutaneous coronary intervention.
Who can participate?
Adults between 18 and 85 years with stable angina who are having an angioplasty
What does the study involve?
Participants are randomly allocated to one of two groups. Starting one day after their surgery, participants in the first group are given 70ml of beetroot juice containing a concentration of 4-5mmol nitrate every day for 6 months. Starting one day after their surgery, participants in the second group are given 70ml nitrate-depleted beetroot juice (where the nitrate has been removed from the juice) to drink every day for 6 months. At the end of the 6 months, participants in both groups are scanned to find out if there is any sign of restenosis.
What are the possible benefits and risks of participating?
Participants in the nitrate group could potentially benefit from an improvement to their cardiovascular (heart and blood vessels) health. There are no notable risks of participating in this study.
Where is the study run from?
William Harvey Research Institute, Queen Mary University of London (UK)
When is the study starting and how long is it expected to run for?
November 2015 to April 2018
Who is funding the study?
National Institute for Health Research (UK)
Who is the main contact?
Dr Krishnaraj Rathod
Trial website
Additional identifiers
EudraCT number
ClinicalTrials.gov number
NCT02529189
Protocol/serial number
20060
Study information
Scientific title
A randomised, double-blind, placebo-controlled study investigating the effects of dietary nitrate on vascular function, platelet reactivity and restenosis in stable angina
Acronym
NITRATE-OCT
Study hypothesis
The aim of this study is to investigate whether dietary nitrate might be useful in preventing restenosis in patients who have undergone elective angioplasty.
Ethics approval
City Road & Hampstead Research Ethics Committee, 22/05/2015, ref: 15/LO/055
Study design
Prospective randomised single-centre double-blind placebo-controlled trial
Primary study design
Interventional
Secondary study design
Randomised controlled trial
Trial setting
Other
Trial type
Treatment
Patient information sheet
Not available in web format, please use the contact details below to request a patient information sheet
Condition
Topic: Cardiovascular disease; Subtopic: Cardiovascular (all Subtopics); Disease: Cardiovascular Prevention
Intervention
Participants are randomly allocated to one of two groups:
Group 1: Participants receive 70ml beetroot juice concentrate containing 4-5mmol nitrate to drink daily, starting one day after their angioplasty procedure for 6 months.
Group 2: Participants receive 70ml beetroot juice which is nitrate-depleted to drink daily, starting one day after their angioplasty procedure for 6 months.
Intervention type
Other
Phase
Phase II
Drug names
Primary outcome measure
Late-lumen loss within the stent is measured using optical coherence tomography (OCT) at 6 months.
Secondary outcome measures
1. Improvement in endothelial function assessed by flow-mediated dilatation of the brachial artery at baseline and 6 months
2. Reduction in target vessel revascularisation (TVR), restenosis rate (diameter >50%) and in-segment late loss is measured using angiography at 6 months (+/- 1 month)
3. Reduction in major adverse cardiac events (i.e. MI, death, CVA, TVR) is measured using via a telephone call at 6, 12 and 24 months
4. Reduction in plaque size as assessed using OCT at 6 months (+/- 1 month)
5. Reduction in inflammatory markers and changes in plasma xanthine oxidase activity, hsCRP and IL-6 is measured using ELISAs at baseline, 6 and 12 months
6. Reduction in platelet count is measured using a blood test at baseline, 6 months and 12 months
Overall trial start date
02/11/2015
Overall trial end date
02/04/2018
Reason abandoned (if study stopped)
Eligibility
Participant inclusion criteria
1. Aged between 18 and 85
2. Able and willing to provide informed consent
3. Patients undergoing successful PCI procedure
4. Patients with stable angina diagnosed by a cardiologist on optimal medical therapy, undergoing an angioplasty to treat residual symptoms
Participant type
Patient
Age group
Adult
Gender
Both
Target number of participants
Planned Sample Size: 246; UK Sample Size: 246
Participant exclusion criteria
1. Unstable ischaemic heart disease, with an episode of chest pain less than 24 hours
2. In patients who have had previous coronary artery bypass surgery (CABG), if they are undergoing angioplasty within a non-native vessel
3. Patients undergoing angioplasty with a bio-absorbable stent
4. Current diagnosis of or treatment for malignancy, other than nonmelanoma skin cancer
5. Current lifethreatening condition other than vascular disease that may prevent a subject completing the study
6. Use of an investigational device or investigational drug within 30 days or 5 half-lives (whichever is the longer) preceding the first dose of study medication
7. Patients considered unsuitable to participate by the research team (e.g., due to medical reasons, laboratory abnormalities, or subject’s unwillingness to comply with all study related procedures)
8. Severe acute infection, or significant trauma (burns, fractures)
9. Pregnancy (tested by urine HcG measurement)
10. History of alcohol or drug abuse within the past 6 months
11. A history of heart failure NYHA class 34 or severe LV dysfunction LVEF<30% regardless of symptom status
12. Systemic autoimmune disease such as rheumatoid arthritis, connective tissue disease, or other conditions known to be associated with chronic inflammation such as inflammatory bowel disease
13. Patients who have donated > 500mls blood within 56 days prior to study medication administration
14. Anaemia with Hb <10g/dl, or any other known blood disorder or significant illness that may affect platelet function, and coagulation
15. A history of chronic viral hepatitis (including presence of hepatitis B surface antigen or hepatitis C antibody or other chronic hepatic disorder) or HIV
16. Abnormal liver function due to acute or chronic liver conditions 3 x upper limit of normal at screening
17. Renal impairment with creatinine clearance (eGFR) of 30ml/min at screening
18. If patients are on mouthwash, they must be willing to stop using this at least 1 week before the start of the study and throughout the duration that they are involved within the study
Recruitment start date
02/11/2015
Recruitment end date
02/04/2018
Locations
Countries of recruitment
United Kingdom
Trial participating centre
William Harvey Research Institute
Barts and the London
Queen Mary University of London
Charterhouse Square
London
EC1M 6BQ
United Kingdom
Funders
Funder type
Government
Funder name
National Institute for Health Research
Alternative name(s)
NIHR
Funding Body Type
government organisation
Funding Body Subtype
Federal/National Government
Location
United Kingdom
Results and Publications
Publication and dissemination plan
All relevant data from this study will be submitted to peer review journals for publication following the end of the study.
Intention to publish date
01/08/2018
Participant level data
Not expected to be available
Basic results (scientific)
Publication list
2016 protocol in: https://www.ncbi.nlm.nih.gov/pubmed/27998900 (added 10/04/2019)