Clinical trial NCT03072199: Rituximab in Patients With Acute ST-elevation Myocardial Infarction Study
Official title: Rituximab in Patients With Acute ST-elevation Myocardial Infarction Study
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: PHASE1
PHASE2
Conditions: Ischemic Heart Disease
Myocardial Infarction
Inflammation
Keywords: Rituximab
B cells
Lead sponsor: Papworth Hospital NHS Foundation Trust
Sponsor class: OTHER_GOV
First posted: 2017-03-07
Enrollment: 24
Sex: ALL
Minimum age (years): 18
Maximum age (years): 75
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Phase 1/2 unblinded interventional dose escalation study
Primary purpose: TREATMENT

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.


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

Primary outcomes:
measure: Safety - Review of Adverse Events and Serious Adverse Events;
timeFrame: 6month
measure: Safety - Clinically significant changes in biochemical and haematological markers
timeFrame: 6month
measure: Safety - Clinically significant ECG changes
timeFrame: 6month
Secondary outcomes:
measure: B cells
timeFrame: Days 0, 6, 14 and 6months
measure: Cardiac biomarkers - Circulating inflammatory (hsCRP and IL6) and cardiovascular (BNP and Troponin) biomarkers.
timeFrame: Days 0, 2 and 6 months
Other outcomes:
Locations:
city: Cambridge
country: United Kingdom
facility: Papworth Hospital NHS Trust
state: Cambridgeshire
Study officials:
References:
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.