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

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
ClinicalTrials.gov Identifier: NCT03072199
Recruitment Status : Active, not recruiting
First Posted : March 7, 2017
Last Update Posted : March 25, 2019
Sponsor:
Information provided by (Responsible Party):
Papworth Hospital NHS Foundation Trust

Tracking Information
First Submitted Date  ICMJE February 24, 2017
First Posted Date  ICMJE March 7, 2017
Last Update Posted Date March 25, 2019
Actual Study Start Date  ICMJE June 1, 2017
Actual Primary Completion Date March 1, 2019   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: March 8, 2017)
  • 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.
  • 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.
  • 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.
Original Primary Outcome Measures  ICMJE
 (submitted: March 1, 2017)
  • 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 studies patients whilst they are an inpatient. Subsequently patient 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 [ 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.
  • 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.
Change History Complete list of historical versions of study NCT03072199 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: March 8, 2017)
  • 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)
  • 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
Original Secondary Outcome Measures  ICMJE
 (submitted: March 1, 2017)
  • B cells [ Time Frame: 6 month ]
    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. [ Time Frame: 6 months ]
    These will be measure before the infusion and compared to after infusion on days 2, 6 and 6 months
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Rituximab in Patients With Acute ST-elevation Myocardial Infarction Study
Official Title  ICMJE Rituximab in Patients With Acute ST-elevation Myocardial Infarction Study
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.

Detailed Description Not Provided
Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Phase 2
Study Design  ICMJE Intervention Model: Single Group Assignment
Intervention Model Description:
Phase 1/2 unblinded interventional dose escalation study
Masking: None (Open Label)
Primary Purpose: Treatment
Condition  ICMJE
  • Ischemic Heart Disease
  • Myocardial Infarction
  • Inflammation
Intervention  ICMJE Drug: RiTUXimab Injection
Single dose of Rituximab given intravenously within 48hours of myocardial infarction
Study Arms  ICMJE Experimental: Rituximab
Intervention: Drug: RiTUXimab Injection
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Active, not recruiting
Estimated Enrollment  ICMJE
 (submitted: March 1, 2017)
24
Original Estimated Enrollment  ICMJE Same as current
Estimated Study Completion Date  ICMJE September 1, 2019
Actual Primary Completion Date March 1, 2019   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 18 Years to 75 Years   (Adult, Older Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE United Kingdom
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT03072199
Other Study ID Numbers  ICMJE P02100
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product
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
IPD Sharing Statement  ICMJE
Plan to Share IPD: No
Responsible Party Papworth Hospital NHS Foundation Trust
Study Sponsor  ICMJE Papworth Hospital NHS Foundation Trust
Collaborators  ICMJE Not Provided
Investigators  ICMJE Not Provided
PRS Account Papworth Hospital NHS Foundation Trust
Verification Date March 2019

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP