- ICH GCP
- US Clinical Trials Registry
- Clinical Trial NCT03072199
Rituximab in Patients With Acute ST-elevation Myocardial Infarction Study (RITA-MI)
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.
Study Overview
Status
Intervention / Treatment
Study Type
Enrollment (Actual)
Phase
- Phase 2
- Phase 1
Contacts and Locations
Study Locations
-
-
Cambridgeshire
-
Cambridge, Cambridgeshire, United Kingdom, CB23 3RE
- Papworth Hospital NHS Trust
-
-
Participation Criteria
Eligibility Criteria
Ages Eligible for Study
Accepts Healthy Volunteers
Genders Eligible for Study
Description
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
Study Plan
How is the study designed?
Design Details
- Primary Purpose: Treatment
- Allocation: N/A
- Interventional Model: Single Group Assignment
- Masking: None (Open Label)
Arms and Interventions
Participant Group / Arm |
Intervention / Treatment |
---|---|
Experimental: Rituximab
|
Single dose of Rituximab given intravenously within 48hours of myocardial infarction
|
What is the study measuring?
Primary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
Safety - Review of Adverse Events and Serious Adverse Events;
Time Frame: 6month
|
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.
|
6month
|
Safety - Clinically significant changes in biochemical and haematological markers
Time Frame: 6month
|
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.
|
6month
|
Safety - Clinically significant ECG changes
Time Frame: 6month
|
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.
|
6month
|
Secondary Outcome Measures
Outcome Measure |
Measure Description |
Time Frame |
---|---|---|
B cells
Time Frame: Days 0, 6, 14 and 6months
|
Circulating B cells count before, immediately after administration (30 mins and 6 hours), and extended follow up (6 days, 14 days and 6months)
|
Days 0, 6, 14 and 6months
|
Cardiac biomarkers - Circulating inflammatory (hsCRP and IL6) and cardiovascular (BNP and Troponin) biomarkers.
Time Frame: Days 0, 2 and 6 months
|
These will be measure before the infusion and compared to after infusion on days 2, 6 and 6 months
|
Days 0, 2 and 6 months
|
Collaborators and Investigators
Publications and helpful links
Study record dates
Study Major Dates
Study Start (Actual)
Primary Completion (Actual)
Study Completion (Actual)
Study Registration Dates
First Submitted
First Submitted That Met QC Criteria
First Posted (Actual)
Study Record Updates
Last Update Posted (Actual)
Last Update Submitted That Met QC Criteria
Last Verified
More Information
Terms related to this study
Additional Relevant MeSH Terms
- Ischemia
- Pathologic Processes
- Necrosis
- Cardiovascular Diseases
- Vascular Diseases
- Arteriosclerosis
- Arterial Occlusive Diseases
- Coronary Disease
- Myocardial Infarction
- Infarction
- Heart Diseases
- Coronary Artery Disease
- Myocardial Ischemia
- ST Elevation Myocardial Infarction
- Inflammation
- Physiological Effects of Drugs
- Antirheumatic Agents
- Antineoplastic Agents
- Immunologic Factors
- Antineoplastic Agents, Immunological
- Rituximab
Other Study ID Numbers
- P02100
Plan for Individual participant data (IPD)
Plan to Share Individual Participant Data (IPD)?
Drug and device information, study documents
Studies a U.S. FDA-regulated drug product
Studies a U.S. FDA-regulated device product
product manufactured in and exported from the U.S.
This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.
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