Assessing the blood effects of the immunosuppressant Rituximab in patients with acute heart attacks

Phase 1

• Conditions: Anterior STEMI revascularised by PPCI; MedDRA version: 19.0Level: LLTClassification code 10066641Term: Acute myocardial infarction, of anterior wallSystem Organ Class: 100000004849; Therapeutic area: Diseases [C] - Cardiovascular Diseases [C14]

• Registration Number: EUCTR2016-000211-33-GB
• Lead Sponsor: Papworth Hospital NHS Foundation Trust

Brief Summary

Not available

Detailed Description

Not available

Study Timeline

• Results First Posted: 1900-01-01
• Study Start: 2016-08-17
• Last Update Posted: 27 July 2020

Recruitment & Eligibility

• Status: ot Recruiting
• Sex: All
• Target Recruitment: 24

Inclusion Criteria

1. Age 18-75 years old
2. Acute anterior STEMI and successful primary percutaneous coronary intervention (PCI) with stent inplantation in the culpirt lesion during the first 24hrs after onset of symptoms
3. Provision of written informed consent
Are the trial subjects under 18? no
Number of subjects for this age range: 0
F.1.2 Adults (18-64 years) yes
F.1.2.1 Number of subjects for this age range 16
F.1.3 Elderly (>=65 years) yes
F.1.3.1 Number of subjects for this age range 8

Exclusion Criteria

1. Previous history of STEMI
2. Cardiogenic shock (systolic blood pressure <80mmHg; unresponsive to fluids, or necessitating catecholamines) electrical instability or severe congestive heart failure
3. corrected QT interval >500msecs using Bazett's formula
4. Hematologic abnormalities (hemoglobin <10g/dL or hematocrit <30%, platelet cell count of <100x10(3)/uL, white blood cell count <4x10(3)/uL)
5. Renal failure (estimated GFR by the MDRD formula <45ml/min/1.73m2)
6. Known hepatic failure or abnormal liver function tests at baseline (ALT>2xULN)
7. Active or recurrent hepatitis (type B)
8. Known HIV infection
9. Current or previous tuberculosis (CXR)
10. Current infections
11. Presence or history in the previous five years of an ongoing cancer, except in situe cancer of the cervix or basal cell carcinoma
12. Any oral or intravenous immunosuppressive treatment (other than concomitant 100mg methylprednisolone), disease modifying drugs or other immue modulatory monoclonal antibodies
13. Allergy to rituximab or one of its excipients
14. Expected need for vaccination with a live attenuated vaccine during the study including incomplete vaccination courses
15. Known or suspected preganacy at screening or lactating women
16. Women of childbearing age unless confirmed by direct questioning that they are reproductively sterile or post menopausal
17. Participation in other clinical trials
18. Inability to comply with study procedures

Study & Design

• Study Type: Interventional clinical trial of medicinal product
• Study Design: Not specified

Primary Outcome Measures

Name	Time	Method
Main Objective: To determine the lowest dose of rituximab with the highest biological efficacy (B cell depletion) and the best safety profile (lowest incidence of undesirable effects) in patients with acute anterior myocardial infraction treated by PPCI.;Secondary Objective: To determine the infarct size by serial cardiac biomarker release.;Primary end point(s): To assess the safety of rituximab in ST-elevation myocardial infarction (STEMI) patients by monitoring their response to the drug in a controlled environment and on extended follow up.;Timepoint(s) of evaluation of this end point: Primary outcome measures will be assessed at days 1-6, day 14, day 30 and 6 months post infusion via:<br>• Review of Adverse Events and Serious Adverse Events <br>• Clinically significant changes in biochemical and haematological markers (serum creatinine, eGFR, liver function tests, blood glucose, full blood count and differential)<br>• Clinically significant ECG changes (arrhythmias, ischaemic changes, QTc)<br>

Secondary Outcome Measures

Name	Time	Method
Secondary end point(s): To assess the effect of rituximab on circulating B cells immediately after administration and on extended follow up.;Timepoint(s) of evaluation of this end point: Secondary endopoints i.e. kinetics and extent of reduction of B lymphocyte number in blood post infusion of Rituximab will be assessed at 30 mins, 6 hours, days 6, 14 and 6 months post infusion.