Phase III Study on the Reversal of Ticagrelor with PB2452

Austria, Belgium, Canada, China, France, Germany, Italy, Netherlands, Spain, Sweden, Switzerland, United Kingdom, United States (ICTRP)

ID di studio ICTRP
NCT04286438 (ICTRP)

Titolo ufficiale (approvato dal comitato etico)
A Phase 3, Multicenter, Open-Label, Single-Arm Study of PB2452 in Ticagrelor-Treated Patients with Uncontrolled Major or Life-Threatening Bleeding or Requiring Urgent Surgery or Invasive Procedure (BASEC)

Titolo accademico
A Phase 3, Multicenter, Open-Label, Single-Arm Study of Bentracimab (PB2452) in Ticagrelor-Treated Patients With Uncontrolled Major or Life-Threatening Bleeding or Requiring Urgent Surgery or Invasive Procedure (REVERSE-IT Trial) (ICTRP)

Titolo pubblico
Bentracimab in Ticagrelor-treated Patients With Uncontrolled Bleeding or Requiring Urgent Surgery or Invasive Procedure (ICTRP)

Malattie studiate
Hemorrhage;Urgent Surgery;Invasive Procedure (ICTRP)

Intervento studiato
Drug: Bentracimab (PB2452) Infusion (ICTRP)

Tipo di studio
Interventional (ICTRP)

Disegno dello studio
Allocation: N/A. Intervention model: Single Group Assignment. Primary purpose: Treatment. Masking: None (Open Label). (ICTRP)

Criteri di inclusione/esclusione
Gender: All
Maximum age: N/A
Minimum age: 18 Years
Inclusion Criteria:

Patients will be eligible for inclusion into the study if they meet all of the following
criteria:

1. Male or female >18 years of age with documented or verbal informed consent.
Emergency consent may be obtained where permitted by local regulations and
institutional approval.

2. History or documentation of ticagrelor intake within the prior 3 days

3. Patients described below who require urgent reversal of the antiplatelet effects of
ticagrelor:

Patients with uncontrolled major or life-threatening bleeding, requiring urgent reversal
of the antiplatelet effects of ticagrelor. It is expected that enrolled patients would
have characteristics similar to those described below:

- Potentially life-threatening bleeding with signs or symptoms of hemodynamic
compromise, e.g., systolic blood pressure < 90 mm Hg and signs or symptoms of low
cardiac output not otherwise explained

- Bleeding in a critical organ or closed space, such as intracranial, intraspinal,
intraocular, retroperitoneal, intra-articular, pericardial, or intramuscular bleed
with compartment syndrome

- Visible, uncontrolled bleeding associated with a corrected hemoglobin level < 8.0
g/dL, a fall in hemoglobin level of = 2.0 g/dL (1.24 mmol/L) from a known baseline,
or requirement for transfusion of 2 or more units of packed red blood cells (PRBC)

Patients requiring urgent surgery or invasive procedure when it is not medically
advisable either to proceed urgently with impaired hemostasis or to delay the urgent
procedure for 3 or more days due to the high risk of bleeding. These patients may
typically be in any of the following clinical situations:

- Requires urgent surgery or invasive procedure known to be associated with a risk of
significant bleeding (such as cardiac surgery, neurosurgery, or major orthopedic
surgery)

- Requires urgent surgery or invasive procedure that may have an adverse procedural
outcome if hemostasis is impaired (such as neurological, spinal, ophthalmological,
urological, or orthopedic surgery)

- At risk of experiencing life-threatening events, such as, shock, myocardial
infarction, or stroke, if significant intraoperative or postoperative bleeding
occurs (such as in elderly patients or patients with underlying cardiac or pulmonary
disease who have limited cardiopulmonary reserve)

Exclusion Criteria:

1. Known sensitivity or contraindication to PB2452 or any of its excipients

2. Patients in whom ticagrelor reversal is not considered urgent, e.g., patients with
stable or non-acute conditions who have low hemoglobin due to chronic, low-grade
gastrointestinal bleeding or who have stable, remote, or asymptomatic intracranial
hemorrhage

3. Patients expected to be clinically unsalvageable, such as, patients with end-stage
cancer or patients with overwhelming sepsis

4. Any condition which, in the opinion of the investigator, would make it unsafe or
unsuitable for the patients to participate in this study. This includes assessment
of likelihood to cooperate with study follow-up visits and procedures. Known
pregnancy may be exclusionary in some regions or countries as directed by national
health authorities and/or local Institutional Review Boards/Ethics Committees

5. Known use of clopidogrel, prasugrel or ticlopidine within 5 days of study drug
administration; known use of antiplatelet GPIIb/IIIa inhibitors, or cangrelor within
5 half-lives of expected study drug administration; or known use of warfarin,
dabigatran, rivaroxaban, apixaban, or edoxaban within 5 half-lives of expected study
drug administration

6. Known recent use (< 5 day) of vitamin K, prothrombin complex concentrate,
recombinant factor VIIa, idarucizumab, or andexanet-alfa (coagulation factor Xa
(recombinant), inactivated-zhzo) (ICTRP)

non disponibile

Endpoint primari e secondari
Reversal - Platelet Reactivity Units (PRU);Hemostasis - Uncontrolled major of life-threatening bleeding - Achievement;Hemostasis - Urgent surgery or invasive procedure - Achievement (ICTRP)

Minimum % inhibition of Platelet Reactivity Index (PRI) (VASP);Maximum reversal of PRU assessed by VerifyNow? PRUTest?;Maximum reversal of PRI assessed by VASP;Proportion of subjects achieving reversal of platelet inhibition of ticagrelor using PRU and PRI - 60%;Proportion of subjects achieving reversal of platelet inhibition of ticagrelor using PRU and PRI - 80%;Proportion of subjects achieving reversal of platelet inhibition of ticagrelor using PRU and PRI - 100%;Duration of at least 60% reversal by PRU and PRI;Duration of at least 80% reversal by PRU and PRI;Duration of at least 100% reversal by PRU and PRI;Intracranial hemorrhage (ICH) Patients Only: Proportion of ICH patients with modified Rankin Scale (mRS) score of 0-3 versus 4-6 at 90 days on a scale of 0-6 (better to worse);ICH Patients Only: Absolute and percent change form baseline in modified Rankin Scale (mRS) score at 90 days in ICH patients on a scale of 0-6 (better to worse);ICH Patients Only: EQ-5D 5L Quality of Life Questionnaire index at 90 days and change from baseline in ICH patients on a scale of 0-100 (best to worst) (ICTRP)

Data di registrazione
non disponibile

Inclusione del primo partecipante
non disponibile

Sponsor secondari
non disponibile

Contatti aggiuntivi
Deepak Bhatt, MD, MPH, Brigham and Women's Hospital, Division of Cardiovascular Medicine (ICTRP)

ID secondari
2019-004457-92, PB2452-PT-CL-0004 (ICTRP)

Risultati-Dati individuali dei partecipanti
non disponibile

Ulteriori informazioni sullo studio
https://clinicaltrials.gov/ct2/show/NCT04286438 (ICTRP)