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Rituximab in Patients With Acute ST-elevation Myocardial Infarction Study (RITA-MI)

Primary Purpose

Ischemic Heart Disease, Myocardial Infarction, Inflammation

Status
Completed
Phase
Phase 1
Locations
United Kingdom
Study Type
Interventional
Intervention
RiTUXimab Injection
Sponsored by
Papworth Hospital NHS Foundation Trust
About
Eligibility
Locations
Arms
Outcomes
Full info

About this trial

This is an interventional treatment trial for Ischemic Heart Disease focused on measuring Rituximab, B cells

Eligibility Criteria

18 Years - 75 Years (Adult, Older Adult)All SexesDoes not accept healthy volunteers

Inclusion Criteria:

  • Age 18-75 years old
  • Acute anterior (left anterior descending artery) STEMI and successful primary percutaneous coronary intervention (PCI) with stent implantation in the culprit lesion during the first 24h after onset of symptoms

Exclusion Criteria:

  • A previous history of STEMI
  • Cardiogenic shock (systolic blood pressure <80 mm Hg, unresponsive to fluids, or necessitating catecholamines), electrical instability or severe congestive heart failure
  • Residual severe proximal bystander disease awaiting inpatient revascularisation
  • Corrected QT interval (QTc) > 500 msecs using Bazett's formula
  • Hematologic abnormalities (hemoglobin <10 g/dL or hematocrit <30%, platelet cell count of <100 x103/μL, white blood cell count <4 x103/μL)
  • Hypogammaglobulinaemia (defined as <3g/L of IgG)
  • Renal failure (estimated GFR by the MDRD formula < 45 ml/min/1.73m2);
  • Known hepatic failure or abnormal liver function tests at baseline (ALT > 2 x ULN).
  • Active or recurrent hepatitis (type B).
  • Known HIV infection
  • Current or previous tuberculosis (Chest X-Ray)
  • Current infections
  • Presence or history in the previous five years of an ongoing cancer, except in situ cancer of the cervix or basal cell carcinoma
  • Any oral or intravenous immunosuppressive treatment (other than concomitant 100 mg methylprednisolone), disease modifying drugs, or other immune modulatory monoclonal antibodies or immunodepleting therapy at any time
  • Allergy to rituximab or one of its excipients
  • Expected need for vaccination with a live attenuated vaccine during the study including incomplete vaccination courses.
  • Known or suspected pregnancy at screening or lactating woman
  • Women of childbearing age unless confirmed by direct questioning that they are reproductively sterile or post-menopausal
  • Participation in other clinical trials
  • Inability to comply with study procedures

Sites / Locations

  • Papworth Hospital NHS Trust

Arms of the Study

Arm 1

Arm Type

Experimental

Arm Label

Rituximab

Arm Description

Outcomes

Primary Outcome Measures

Safety - Review of Adverse Events and Serious Adverse Events;
Adverse and serious adverse events will be reviewed by daily history taking and clinical examination of patients whilst they are an inpatient. Subsequently patients will be followed up on discharge daily until day 6 with telephone follow up. On days 6, 14 and 6month patients will be assess again in an outpatient setting where adverse events will be documented. There is additional follow telephone follow up at day 30. After each group of 6 patients are recruited and infused with rituximab, an independent Data and Safety Monitoring Board will review the clinical and biological data and their side effect profile, including adverse events.
Safety - Clinically significant changes in biochemical and haematological markers
Biochemistry and haematology bloods will be taken daily after drug administration whilst an inpatient. Upon discharge bloods will be taken on days 6, 14 and 6month for further assessment. Any new abnormalities will be flagged. After each group of 6 patients are recruited and infused with rituximab, an independent Data and Safety Monitoring Board will review the clinical and biological data and their side effect profile, including adverse events.
Safety - Clinically significant ECG changes
Arrhythmia will be assess as patients will have continued cardiac monitoring whilst an inpatient. ECGs will be performed daily whilst an inpatient and also during outpatient attendance. QTc will be assessed using the Bazett formula. After each group of 6 patients are recruited and infused with rituximab, an independent Data and Safety Monitoring Board will review the clinical and biological data and their side effect profile, including adverse events.

Secondary Outcome Measures

B cells
Circulating B cells count before, immediately after administration (30 mins and 6 hours), and extended follow up (6 days, 14 days and 6months)
Cardiac biomarkers - Circulating inflammatory (hsCRP and IL6) and cardiovascular (BNP and Troponin) biomarkers.
These will be measure before the infusion and compared to after infusion on days 2, 6 and 6 months

Full Information

First Posted
February 24, 2017
Last Updated
September 13, 2021
Sponsor
Papworth Hospital NHS Foundation Trust
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1. Study Identification

Unique Protocol Identification Number
NCT03072199
Brief Title
Rituximab in Patients With Acute ST-elevation Myocardial Infarction Study
Acronym
RITA-MI
Official Title
Rituximab in Patients With Acute ST-elevation Myocardial Infarction Study
Study Type
Interventional

2. Study Status

Record Verification Date
September 2021
Overall Recruitment Status
Completed
Study Start Date
June 1, 2017 (Actual)
Primary Completion Date
March 1, 2019 (Actual)
Study Completion Date
May 1, 2021 (Actual)

3. Sponsor/Collaborators

Responsible Party, by Official Title
Sponsor
Name of the Sponsor
Papworth Hospital NHS Foundation Trust

4. Oversight

Studies a U.S. FDA-regulated Drug Product
No
Studies a U.S. FDA-regulated Device Product
No
Product Manufactured in and Exported from the U.S.
No
Data Monitoring Committee
Yes

5. Study Description

Brief Summary
RITA-MI aims to develop of a novel therapeutic concept to target the immune response in patients with acute myocardial infarction (MI) by depleting B-cells with a single injection of Rituximab which is approved for clinical use in cancer, autoimmune disease and inflammatory conditions. The goal is to re-purpose the drug, and translate the discovery into benefit for patients at high risk of cardiovascular events. Rituximab is expected to limit infarction size and improve the healing process, as complementary to other therapeutic strategies. The applicants intend to perform a clinical study in patients with acute myocardial infarction (MI). The objective is to find the optimal dose (lowest dose with highest biological efficacy and best safety profile) for peripheral blood B cell depletion during the first 6 days after injection, and selective molecular signatures associated with improved heart function through analysis of peripheral blood samples. The study rationale is to decrease the inflammatory reaction upon tissue necrosis following heart muscle ischemia.

6. Conditions and Keywords

Primary Disease or Condition Being Studied in the Trial, or the Focus of the Study
Ischemic Heart Disease, Myocardial Infarction, Inflammation
Keywords
Rituximab, B cells

7. Study Design

Primary Purpose
Treatment
Study Phase
Phase 1, Phase 2
Interventional Study Model
Single Group Assignment
Model Description
Phase 1/2 unblinded interventional dose escalation study
Masking
None (Open Label)
Allocation
N/A
Enrollment
24 (Actual)

8. Arms, Groups, and Interventions

Arm Title
Rituximab
Arm Type
Experimental
Intervention Type
Drug
Intervention Name(s)
RiTUXimab Injection
Intervention Description
Single dose of Rituximab given intravenously within 48hours of myocardial infarction
Primary Outcome Measure Information:
Title
Safety - Review of Adverse Events and Serious Adverse Events;
Description
Adverse and serious adverse events will be reviewed by daily history taking and clinical examination of patients whilst they are an inpatient. Subsequently patients will be followed up on discharge daily until day 6 with telephone follow up. On days 6, 14 and 6month patients will be assess again in an outpatient setting where adverse events will be documented. There is additional follow telephone follow up at day 30. After each group of 6 patients are recruited and infused with rituximab, an independent Data and Safety Monitoring Board will review the clinical and biological data and their side effect profile, including adverse events.
Time Frame
6month
Title
Safety - Clinically significant changes in biochemical and haematological markers
Description
Biochemistry and haematology bloods will be taken daily after drug administration whilst an inpatient. Upon discharge bloods will be taken on days 6, 14 and 6month for further assessment. Any new abnormalities will be flagged. After each group of 6 patients are recruited and infused with rituximab, an independent Data and Safety Monitoring Board will review the clinical and biological data and their side effect profile, including adverse events.
Time Frame
6month
Title
Safety - Clinically significant ECG changes
Description
Arrhythmia will be assess as patients will have continued cardiac monitoring whilst an inpatient. ECGs will be performed daily whilst an inpatient and also during outpatient attendance. QTc will be assessed using the Bazett formula. After each group of 6 patients are recruited and infused with rituximab, an independent Data and Safety Monitoring Board will review the clinical and biological data and their side effect profile, including adverse events.
Time Frame
6month
Secondary Outcome Measure Information:
Title
B cells
Description
Circulating B cells count before, immediately after administration (30 mins and 6 hours), and extended follow up (6 days, 14 days and 6months)
Time Frame
Days 0, 6, 14 and 6months
Title
Cardiac biomarkers - Circulating inflammatory (hsCRP and IL6) and cardiovascular (BNP and Troponin) biomarkers.
Description
These will be measure before the infusion and compared to after infusion on days 2, 6 and 6 months
Time Frame
Days 0, 2 and 6 months

10. Eligibility

Sex
All
Minimum Age & Unit of Time
18 Years
Maximum Age & Unit of Time
75 Years
Accepts Healthy Volunteers
No
Eligibility Criteria
Inclusion Criteria: Age 18-75 years old Acute anterior (left anterior descending artery) STEMI and successful primary percutaneous coronary intervention (PCI) with stent implantation in the culprit lesion during the first 24h after onset of symptoms Exclusion Criteria: A previous history of STEMI Cardiogenic shock (systolic blood pressure <80 mm Hg, unresponsive to fluids, or necessitating catecholamines), electrical instability or severe congestive heart failure Residual severe proximal bystander disease awaiting inpatient revascularisation Corrected QT interval (QTc) > 500 msecs using Bazett's formula Hematologic abnormalities (hemoglobin <10 g/dL or hematocrit <30%, platelet cell count of <100 x103/μL, white blood cell count <4 x103/μL) Hypogammaglobulinaemia (defined as <3g/L of IgG) Renal failure (estimated GFR by the MDRD formula < 45 ml/min/1.73m2); Known hepatic failure or abnormal liver function tests at baseline (ALT > 2 x ULN). Active or recurrent hepatitis (type B). Known HIV infection Current or previous tuberculosis (Chest X-Ray) Current infections Presence or history in the previous five years of an ongoing cancer, except in situ cancer of the cervix or basal cell carcinoma Any oral or intravenous immunosuppressive treatment (other than concomitant 100 mg methylprednisolone), disease modifying drugs, or other immune modulatory monoclonal antibodies or immunodepleting therapy at any time Allergy to rituximab or one of its excipients Expected need for vaccination with a live attenuated vaccine during the study including incomplete vaccination courses. Known or suspected pregnancy at screening or lactating woman Women of childbearing age unless confirmed by direct questioning that they are reproductively sterile or post-menopausal Participation in other clinical trials Inability to comply with study procedures
Facility Information:
Facility Name
Papworth Hospital NHS Trust
City
Cambridge
State/Province
Cambridgeshire
ZIP/Postal Code
CB23 3RE
Country
United Kingdom

12. IPD Sharing Statement

Plan to Share IPD
No
Citations:
PubMed Identifier
33783498
Citation
Zhao TX, Aetesam-Ur-Rahman M, Sage AP, Victor S, Kurian R, Fielding S, Ait-Oufella H, Chiu YD, Binder CJ, Mckie M, Hoole SP, Mallat Z. Rituximab in patients with acute ST-elevation myocardial infarction: an experimental medicine safety study. Cardiovasc Res. 2022 Feb 21;118(3):872-882. doi: 10.1093/cvr/cvab113.
Results Reference
derived

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Rituximab in Patients With Acute ST-elevation Myocardial Infarction Study

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