NITRITE/AMI/4.1

Barts and the London NHS Trust

5 Walden Street, London, United Kingdom, E1 2EF

Professor Anthony Mathur, Barts and the London NHS Trust, 0044 20 8983 2216 , a.mathur@qmul.ac.uk

Professor Anthony Mathur, Barts and the London NHS Trust, 0044 20 8983 2216 , a.mathur@qmul.ac.uk

No

No

No

Final

30 Nov 2015

No

Yes

09 Feb 2017

No

To determine whether the intracoronary delivery of nitrite in patients undergoing primary percutaneous coronary angioplasty (PPCI) for acute myocardial infarction (heart attack) decreases the amount of damage caused by the heart attack (as measured by levels of damage detected in blood tests)

1). The risks from the IMP are low. Sodium and nitrite are endogenously­ occurring ions with no immunological potential, therefore there is no risk of an allergic reaction. The small volume of 1.8micromol in 10 ml of saline given over 30 seconds is very unlikely to pose any problems. 2). Possible Delay in Door to Balloon inflation time. The delivery of the IMP (sodium nitrite) down the coronary artery will lead to a small delay in balloon inflation. There are studies demonstrating that any delay in door­to­balloon time for patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention is associated with higher mortality, even among patients treated within 90 minutes of admission. Our institution sets internal targets of <60 minutes for door to balloon time. Any possible delay has been minimised by 1). the wire will have already been passed down the coronary artery possibly restoring some epicardial flow 2). the nitrite infusion will be delivered down an over the wire balloon so that immediately after infusion the balloon can be inflated restoring flow if necessary otherwise an export catheter will be used to aspirate thrombus first 3). the time of the infusion has been kept to 30 seconds meaning at most there should be a delay of 1­2 minutes in the door to balloon time. 3). CMR scan − the CMR scan does not use radiation. There are no major known side effects or risks attached to CMR although some patients may find it a little claustraphobic. The main issues are related to possible allergy to contrast agent and the scanning process. Most CMR exams are painless, however, some patients find it uncomfortable t

01 Nov 2011

No

Yes

United Kingdom: 82

82

82

0

0

0

0

0

0

54

28

0

Overall trial (overall period)

Randomised - controlled

The IMP was allocated a specific number identifier, which only the manufacturer and pharmacy team knew. The study team and patient did not know which IMP contained the active ingredient. The master list for the IMP was securely stored in by the pharmacy team who were also responsible for unblinding the patients. A independent randomisation algorithm was used to allocate the IMP identifier aiming for a 1:1 allocation in 82 patients.

Yes

Sodium Nitrite (1.8micromol in 10mls N/Saline)

Injection

Intracoronary use

1.8micromols Sodium Nitrite in 10 mls N/Saline

Placebo (10mls N/saline)

Injection

Intracoronary use

10 mls of N/Saline

Overall trial

Active arm

Control Arm

Primary

Creatine Kinase AUC measured over 48 hours

This endpoint was assessed using the Wilcoxon Rank Sum test as non-paramteric data

Control Arm v Active arm

66

Post-hoc

Adverse events were reported for all consented patients until the end of the study. AE and SAE were reported to the sponsor within 24 hours of the site becoming aware of them. Supporting documentation were provided as soon as possible

Supporting documentation were provided as soon as possible. The DSMB met every 3 months during the recruitment phase of the study and then twice yearly. The independent members were aware of the recruitment rate/AS and SAE. All events were assessed and adjudicated.

10.0

Active arm

Control Arm