NITRATE-OCT-CIN (Sub-Study of NITRATE-OCT)

NCT05544981 | Completed DMC

• 1 other identifier: 17/SC/0020
• Study Type: interventional
• Target: 300
• Locations: 1 country
• Sites: 1

Brief Summary

The NITRATE-OCT:- Contrast Nephropathy Sub-study is a proof-of concept single center, randomized, clinical trial designed to ascertain whether a dietary NO3- approach might prove useful adjunctive therapy improving renal function and reducing CIN in patients with stable angina undergoing elective angioplasty. Objectives: To determine whether dietary NO3- ingestion exerts any effect on the glomerular filtration rate (GFR) after the exposure to contrast media. To determine if dietary NO3- ingestion will decrease the incidence of contrast induced nephropathy. Setting: The patients will be recruited from an on-going clinical trial NITRATE-OCT. This is a study assessing whether the use of dietary NO3- may reduce the incidence of restenosis following elective angioplasty. This study is recruiting patients with stable angina and single/multiple coronary artery stenosis undergoing elective PCI who are haemodynamically stable (systolic BP\>100 mmHg). These patients will be recruited at The Barts Heart Centre at St Bartholomew's Hospital. This is one of the biggest centres in the UK, serving a population of almost two million people from The City of London and The North East up to the M25 and is a 24/7 centre performing approximately 3000 angioplasties a year. The study will take place in the Clinical Trials Unit, William Harvey Heart Centre. Target population: A total of 246 patients (male and female, age 18-85) with stable angina as per requirements indicated above. Follow-up will take place in the Clinical Trials Unit, William Harvey Research Institute. Treatment: Patients will be randomised (using an on line randomisation database) to receive 70 ml of a beetroot juice concentrate containing 4-5 mmol nitrate or nitrate-depleted placebo juice concentrate. This intervention will be taken by the patient daily from one day prior to re-establishment of flow with PCI and stent implantation.

Conditions

Cardiovascular Diseases

Keywords

Stable Angina; Nitrate; Contrast Induced Nephropathy

Outcome Measures

Primary Outcomes (1)

• Incidence of CIN

  The primary endpoint will be the incidence of CIN (defined as an absolute rise of ≥0.5 mg/dL or a relative increase of ≥25% in serum creatinine over baseline within 48 to 72 h after contrast administration) We will compare the incidence of CIN in patients who received oral nitrate with the of the group that did not receive nitrates.

  2-3 days post procedure (as Per KDIGO)

Secondary Outcomes (3)

• Change in eGFR from pre to post procedure (within 48hours)

  2 days post procedure

• Incidence of Re-hospitalization, haemodialysis and mortality

  6 weeks after contrast admistration

• Plasma levels of NGAL, cystatin-C and measured at 24-72 hours post contrast administration.

  2-3 days post procedure

Study Arms (2)

Nitrate-rich beetroot juice

ACTIVE COMPARATOR

70 ml of a beetroot juice concentrate containing \~5 mmol nitrate

Dietary Supplement: Beetroot Juice

Nitrate-deplete beetroot juice

PLACEBO COMPARATOR

70 ml of a beetroot juice concentrate that is nitrate-depleted

Dietary Supplement: Beetroot Juice

Interventions

Beetroot Juice DIETARY_SUPPLEMENT

70 ml of beetroot juice containing \~5 mmol of inorganic nitrate

Nitrate-rich beetroot juice

Eligibility Criteria

• Age: 18 Years - 85 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients with stable angina diagnosed by a cardiologist on optimal medical therapy undergoing angioplasty to treat residual symptoms.
• Aged 18-85
• Patients able and willing to give their written informed consent.
• Patients undergoing successful PCI procedure.

You may not qualify if:

• Unstable ischaemic heart disease, with an episode of chest pain in less than 24 hours.
• Patients who have had previous coronary artery bypass surgery (CABG), if they are undergoing angioplasty within a non-native vessel.
• Patients undergoing angioplasty with a bio-absorbable stent.
• Current diagnosis of or treatment for malignancy, other than non-melanoma skin cancer.
• Current life-threatening condition other than vascular disease that may prevent a subject completing the study.
• 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.
• 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).
• Severe acute infection, or significant trauma (burns, fractures).
• Pregnancy. This will be tested by urine HcG measurement
• History of alcohol or drug abuse within the past 6 months.
• A history of heart failure NYHA class 3-4 or severe LV dysfunction LVEF\<30% regardless of symptom status.
• 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.
• Patients who have donated \> 500mls blood within 56 days prior to study medication administration.
• Anaemia with Hb \<10g/dl, or any other known blood disorder or significant illness that may affect platelet function, and coagulation.
• A history of chronic viral hepatitis (including presence of hepatitis B surface antigen or hepatitis C antibody or other chronic hepatic disorder) or HIV.

Sponsors & Collaborators

• Queen Mary University of London: lead

Study Sites (1)

William Harvey Research Institute, Barts and The London School of Medicine

London, EC1M 6BQ, United Kingdom

Location

Related Publications (2)

• Rathod KS, Jones DA, Van-Eijl TJ, Tsang H, Warren H, Hamshere SM, Kapil V, Jain AK, Deaner A, Poulter N, Caulfield MJ, Mathur A, Ahluwalia A. Randomised, double-blind, placebo-controlled study investigating the effects of inorganic nitrate on vascular function, platelet reactivity and restenosis in stable angina: protocol of the NITRATE-OCT study. BMJ Open. 2016 Dec 20;6(12):e012728. doi: 10.1136/bmjopen-2016-012728.

  PMID: 27998900 BACKGROUND

• Tripatara P, Patel NS, Webb A, Rathod K, Lecomte FM, Mazzon E, Cuzzocrea S, Yaqoob MM, Ahluwalia A, Thiemermann C. Nitrite-derived nitric oxide protects the rat kidney against ischemia/reperfusion injury in vivo: role for xanthine oxidoreductase. J Am Soc Nephrol. 2007 Feb;18(2):570-80. doi: 10.1681/ASN.2006050450. Epub 2007 Jan 3.

  PMID: 17202421 BACKGROUND

MeSH Terms

Conditions

Cardiovascular Diseases; Angina, Stable

Condition Hierarchy (Ancestors)

Angina Pectoris; Myocardial Ischemia; Heart Diseases; Vascular Diseases; Chest Pain; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Daniel A Jones, MBBS, PhD

  Queen Mary University of London

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: April 9, 2019
• First Posted: September 19, 2022
• Study Start: January 2, 2016
• Primary Completion: December 2, 2022
• Study Completion: December 31, 2022
• Last Updated: June 5, 2023

Record last verified: 2022-02

Locations

GB (1)