HemorrhagePhase 3REVERSE-ITNCT04286438
Bentracimab in Ticagrelor-treated Patients With Uncontrolled Bleeding or Requiring Urgent Surgery or Invasive Procedure
A Phase 3 study testing Bentracimab (PB2452) Infusion in people with Hemorrhage and Urgent Surgery, run by SFJ Pharmaceuticals, Inc. at 68 sites in 13 countries.
Trial summary
This is a multi-center, open-label, prospective single-arm study of reversal of the antiplatelet effects of ticagrelor with bentracimab (PB2452) in patients who present with uncontrolled major or life-threatening bleeding or who require urgent surgery or invasive procedure. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemorrhage, Urgent Surgery, Invasive Procedure
- What is being tested?
- Bentracimab (PB2452) Infusion
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 226 participants
- Where
- 68 sitesin 13 countries
- Study dates
- 15 Jul 2020to 9 Sep 2024
- Phase
- Phase 3
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Patients will be eligible for inclusion into the study if they meet all of the following criteria:
- 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.
- History or documentation of ticagrelor intake within the prior 3 days
- 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
Show all 12Show fewer
- 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)
Who cannot join
- Known sensitivity or contraindication to PB2452 or any of its excipients
- 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
- Patients expected to be clinically unsalvageable, such as, patients with end-stage cancer or patients with overwhelming sepsis
- 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
- 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
- Known recent use (< 5 day) of vitamin K, prothrombin complex concentrate, recombinant factor VIIa, idarucizumab, or andexanet-alfa (coagulation factor Xa (recombinant), inactivated-zhzo)
Trial locations and contacts
68 sites in 13 countries.
68 sites in 13 countries
China21 sites
Beijing Anzhen Hospital, Capital Medical University
Beijing, Beijing Municipality, 100029
Peking University First Hospital
Beijing, Beijing Municipality, 100034
Peking University People's Hospital
Beijing, Beijing Municipality, 100044
Peking University Third Hospital
Beijing, Beijing Municipality, 100083
The First Hospital of Jilin University
Changchun, Jilin, 130021
The Second Affiliated Hospital of Jilin University
Changchun, Jilin, 130041
Guizhou Provincial People's Hospital
Guiyang, Guizhou, 550002
Sir Run Run Shaw Hospital, Zhejiang University School of Medicine
Hangzhou, Zhejiang, 310000
Medidata
Hangzhou, Zhejiang, 310009
The First Affiliated Hospital of Harbin Medical University
Harbin, Heilongjiang, 150001
Huai'an First People's Hospital
Huai'an, Jiangsu, 223300
Lanzhou University Second Hospital
Lanzhou, Gansu, 730030
The Second Affiliated Hospital of Nanchang University
Nanchang, Jiangxi, 330006
Shanghai General Hospital
Shanghai, 200080
First Affiliated Hospital of Soochow University
Suzhou, Jiangsu, 215031
Tianjin Medical University General Hospital
Tianjin, Tianjin Municipality, 300052
Tianjin Chest Hospital
Tianjin, Tianjin Municipality, 300222
The Central Hospital of Wuhan
Wuhan, Hubei, 430014
Renmin Hospital of Wuhan University
Wuhan, Hubei, 430060
General Hospital of Ningxia Medical University
Yinchuan, Ningxia, 750004
The First Affiliated Hospital of Zhengzhou University
Zhengzhou, Henan, 45000
United States9 sites
Sinai Hospital of Baltimore
Baltimore, Maryland, 21215
Henry Ford Hospital
Detroit, Michigan, 48202
Sanford Medical Center Fargo
Fargo, North Dakota, 58104
University of Florida Health, Jacksonville
Jacksonville, Florida, 32209
University of Kentucky
Lexington, Kentucky, 40536
North Kansas City Hospital
North Kansas City, Missouri, 64116
Rhode Island Hospital
Providence, Rhode Island, 02903
Cox Medical Centers
Springfield, Missouri, 65807
Ascension St. John Clinical Research Institute
Tulsa, Oklahoma, 74104
Canada9 sites
Foothills Medical Centre
Calgary, Alberta, T2N 2T9
William Osler Health System
Etobicoke, Ontario, M9V 1R8
Hamilton Health Sciences Centre
Hamilton, Ontario, L8L 2X2
Kingston Health Science Centre
Kingston, Ontario, ON K7L 2V7
Montreal Heart Institute
Montreal, Quebec, H1T 1C8
York PCI Group, Inc.
Newmarket, Ontario, L3Y 2P7
Saint John Regional Hospital
Saint John, New Brunswick, E2L 4L2
St. Michael's Hospital, Unity Health Toronto
Toronto, Ontario, M5B 1W8
Toronto General Hospital
Toronto, Ontario, M5G 2C4
Belgium5 sites
Algemeen Stedelijk Ziekenhuis (ASZ) Study Center Cardiology
Aalst, East Flanders, 9300
AZ Sint-Jan Brugge-Oostende AV Poli Cardiologie
Bruges, 8000
University Hospital Antwerp Cardiology Department - Clinical Trials
Edegem, 2650
Ziekenhuis Oost-Limburg Study Center Intensive Care
Genk, Limburg, 3600
Jessa Hospital Hartcentrum Hasselt Research Center
Hasselt, 3500
Spain5 sites
Complejo Hospitalario Universitario A Coruna
A Coruña, 15006
Hospital Universitario Vall d'Hebron
Barcelona, 08035
Hospital Universitario 12 de Octubre, Residencia general
Madrid, 28007
Hospital Universitario Vírgen de la Victoria
Málaga, 28040
Hospital Universitario Virgen Macarena
Seville, 41009
France4 sites
CHU de Lille Service USIC, Institut Coeur Poumon
Lille, 59037
Assistance Publique-Hopitaux de Paris (AP-HP) Pitie-Salpetriere Hospital
Paris, 75013
Bichat Hospital, Service de Cardiologie
Paris, 75018
CHRU de Tours - Hopital Trousseau Service de Cardiologie-USCI 2 eme etage
Tours, 37170
Austria3 sites
Medical University Of Graz
Graz, STY, 8036
Klinische Abteilung für Innere Medizin 3 Universitätsklinikum St. Pölten
Sankt Pölten, 3100
Klinik Ottakring 3rd Med Dept, Cardiology and Intensive Care Medicine
Vienna, 1160
Italy3 sites
ASST Monza - Ospedale San Gerardo
Monza, 20090
Azienda Ospedaliero-Universitaria di Parma Cardiologia
Parma, 43126
Istituto Clinico Humanitas UO Cardiologia Clinica e Interventistica
Rozzano, 20089
Netherlands2 sites
Medisch Spectrum Twente
Enschede, Overijssel, 7512 KZ
St Antonius Hospital
Nieuwegein, 3435 CM
Sweden2 sites
Sahlgrenska University Hospital
Gothenburg, 413 45
Skane University Hospital, Department of Cardiology
Lund, 22185
Switzerland2 sites
Universitatsspital Basel Department of Cardiology
Basel, 4031
Cardiocentro Ticino
Lugano, 6900
United Kingdom2 sites
Sheffield Teaching Hospitals, NHS Foundation Trust, Northern General Hospital
Sheffield, S5 7AU
East and North Hertfordshire, NHS Trust, Lister Cardiac Research Office, Cardiology Green Zone, Lister Hospital
Stevenage, Hertfordshire, SG1 4AB
About this study
Official title: 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)
This is a multi-center, open-label, prospective single-arm study of reversal of the antiplatelet effects of ticagrelor with bentracimab (PB2452) in patients who present with uncontrolled major or life-threatening bleeding or who require urgent surgery or invasive procedure.
At least 200 patients will be enrolled from approximately 200 centers in North America, Europe, and Asia-Pacific regions, including mainland China. Patients with reported use of ticagrelor within the prior 3 days who require urgent ticagrelor reversal will be eligible for enrollment. These populations will be enrolled based on separate inclusion criteria.
Read the detailed description
The study will consist of a Screening/Pre-treatment period, an on-site assignment to study treatment and administration, a Follow-up visit on (Day 3+1 and Day 7±1), a Final Follow-up visit (Day 35±3) and a Follow-up visit for intracranial hemorrhage (ICH) only patients (Day 90±10). Infusion of PB2452 will be initiated on Day 1 and will continue for approximately 16 hours for a total of 18 g.
On Day 1, subjects who meet all the inclusion criteria and none of the exclusion criteria will receive an intravenous (IV) infusion comprised of an initial IV bolus of 6 grams (g) infused over 10 minutes for rapid reversal, followed immediately by a 6g IV loading infusion over 4 hours and then a 6 g IV maintenance infusion over 12 hours. This bentracimab (PB2452) regimen is expected to provide immediate reversal of the antiplatelet effects of ticagrelor within 5 minutes of the initiation of infusion that is sustained for 20-24 hours.
In subjects with potential drug interaction from recent concomitant use of moderate or strong CYP3A inhibitors with ticagrelor, an alternative regimen may be used comprising administration of 36 g over an active treatment period of 24 hours and 10 min. (This alternative regimen will be an initial 12 g bolus infusion over 10 minutes, followed immediately by a loading infusion of 12 g over 6 hours which will then be followed by a maintenance regimen of 12 g infused over 18 hours for a total infusion of 36 grams over 24 hours and 10 minutes).
In patients presenting with intracranial hemorrhage (ICH), brain imaging within 2 hours of initiation of study drug and at least one follow-up brain imaging performed 12-24 hours post completion of PB2452 will be required to support adjudication of hemostasis.
All subjects may be discharged from the clinical site between Days 3 and 7 inclusive and will return for a Follow-up visit on Day 7, if already discharged, and on Day 35 (± 3 days). All ICH patients must complete End of Study (EOS) Day 35±3 (Visit 5). ICH patients that agree to participate in the ICH-only-90-day-follow-up visit will have an additional visit on Day 90±10 (Visit 6).
- Conditions
- Hemorrhage, Urgent Surgery, Invasive Procedure
- Being tested
- Bentracimab (PB2452) Infusion
- Keywords
- Bleeding
- Medical subject headings
- Hemorrhage
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Bentracimab (PB2452) InfusionDrug
Bentracimab (PB2452) 18 g Intravenous Infusion over a 16 hour duration.
In subjects with potential drug interaction from recent concomitant use of moderate or strong CYP3A inhibitors with ticagrelor, the active treatment period may be 24 hours and 10 min if receiving the 36g infusion.
In patients presenting with intracranial hemorrhage (ICH), brain imaging within 2 hours of initiation of study drug and at least one follow-up brain imaging performed 12-24 hours post completion of PB2452.
| Study group | Role | What they receive |
|---|---|---|
| Bentracimab (PB2452) Infusion - Open Label Active Drug | Experimental | Bentracimab (PB2452) 18 g Intravenous Infusion over a 16 hour duration. For patients with uncontrolled major or life-threatening bleeding or in need of urgent surgery or invasive procedure. Receives: Drug: Bentracimab (PB2452) Infusion |
What is being measured
The primary outcome is the main question the study is designed to answer.
Reversal - Platelet Reactivity Units (PRU)
Minimum % inhibition of PRU within 4 hours of the initiation of study drug as assessed by VerifyNow™ PRUTest™ platelet function assay
Measured: 4 hours post-initiation of infusion
Hemostasis - Uncontrolled major of life-threatening bleeding - Achievement
Achievement of effective (graded as good or excellent) hemostasis after initiation of PB2452 infusion will be assessed using prespecified criteria for effective hemostasis for visible and non-visible major bleeding [Scale (from best to worst) measured as: Excellent, Good, Poor/None]
Measured: 4 hours post-initiation of infusion
Hemostasis - Urgent surgery or invasive procedure - Achievement
Achievement of effective hemostasis following initiation of PB2452 infusion will be centrally adjudicated using prespecified criteria for effective hemostasis derived from the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) clinical bleeding scale [GUSTO scale (from best to worst): Effective (no bleeding, mild bleeding or moderate bleeding) or Not effective (severe bleeding)]
Measured: 4 hours post-initiation of infusion
Secondary outcomes (12)
Minimum % inhibition of Platelet Reactivity Index (PRI) (VASP)
Minimum % inhibition of PRI assessed by VASP within 4 hours after the initiation of study drug
Measured: 4 hours post-initiation of infusion
Maximum reversal of PRU assessed by VerifyNow™ PRUTest™
Maximum reversal of PRU assessed by VerifyNow™ PRUTest™ within 4 hours after the initiation of study drug.
Measured: 4 hours post-initiation of infusion
Maximum reversal of PRI assessed by VASP
Maximum reversal of PRI assessed by VASP within 4 hours after the initiation of study drug.
Measured: 4 hours post-initiation of infusion
Proportion of subjects achieving reversal of platelet inhibition of ticagrelor using PRU and PRI - 60%
Proportion of subjects achieving 60% reversal of platelet inhibition by ticagrelor using PRU and PRI at any time point during the treatment period
Measured: Any time point between infusion initiation and Day 3 (Pre-dose, 5-10 minutes, 30+5 minutes, 1+0.25 hours, 4+0.25 hours, 12+0.5 hours, 24+1 hours, and Day 3)
Proportion of subjects achieving reversal of platelet inhibition of ticagrelor using PRU and PRI - 80%
Proportion of subjects achieving 80% reversal of platelet inhibition by ticagrelor using PRU and PRI at any time point during the treatment period
Measured: Any time point between infusion initiation and Day 3 (Pre-dose, 5-10 minutes, 30+5 minutes, 1+0.25 hours, 4+0.25 hours, 12+0.5 hours, 24+1 hours, and Day 3)
Proportion of subjects achieving reversal of platelet inhibition of ticagrelor using PRU and PRI - 100%
Proportion of subjects achieving 100% reversal of platelet inhibition by ticagrelor using PRU and PRI at any time point during the treatment period
Measured: Any time point between infusion initiation and Day 3 (Pre-dose, 5-10 minutes, 30+5 minutes, 1+0.25 hours, 4+0.25 hours, 12+0.5 hours, 24+1 hours, and Day 3)
Duration of at least 60% reversal by PRU and PRI
Measured: Any time point between infusion initiation and Day 3 (Pre-dose, 5-10 minutes, 30+5 minutes, 1+0.25 hours, 4+0.25 hours, 12+0.5 hours, 24+1 hours, and Day 3)
Duration of at least 80% reversal by PRU and PRI
Measured: Any time point between infusion initiation and Day 3 (Pre-dose, 5-10 minutes, 30+5 minutes, 1+0.25 hours, 4+0.25 hours, 12+0.5 hours, 24+1 hours, and Day 3)
Duration of at least 100% reversal by PRU and PRI
Measured: Any time point between infusion initiation and Day 3 (Pre-dose, 5-10 minutes, 30+5 minutes, 1+0.25 hours, 4+0.25 hours, 12+0.5 hours, 24+1 hours, and Day 3)
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)
Measured: [Time Frame: Pre-dose, Day 35 and Day 90]
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)
Measured: [Time Frame: Pre-dose, Day 35 and Day 90]
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)
Measured: [Time Frame: Pre-dose, Day 35 and Day 90]
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted27 Feb 2020
- Study start15 Jul 2020
- Primary completion9 Sep 2024
- Study completion9 Sep 2024
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for HemorrhageStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 3
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Enrolment
- 226 participants (actual)
Sponsor and investigators
- Lead sponsor
- SFJ Pharmaceuticals, Inc.
- Sponsor type
- Industry (pharma, biotech, devices)
- Responsible party
- Sponsor
- Investigators
- Deepak Bhatt, MD, MPH, Study chair, Brigham and Women's Hospital, Division of Cardiovascular Medicine
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04286438
- Sponsor's protocol ID
- PB2452-PT-CL-0004
- Other IDs
- 2019-004457-92, 2019
- Acronym
- REVERSE-IT
- Status last verified
- Oct 2024
- First submitted
- 21 Feb 2020
- Last updated
- 21 Oct 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
Publications
Bhatt DL, Pollack CV, Mazer CD, Angiolillo DJ, Steg PG, James SK, Weitz JI, Ramnath R, Arnold SE, Mays MC, Umstead BR, White B, Hickey LL, Jennings LK, Curry BJ, Lee JS, Verma S. Bentracimab for Ticagrelor Reversal in Patients Undergoing Urgent Surgery. NEJM Evid. 2022 Mar;1(3):EVIDoa2100047. doi: 10.1056/EVIDoa2100047. Epub 2021 Dec 1.
PubMed 38319214
Study at a glance
From the registry record, last updated by the sponsor on 21 Oct 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- 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)
- ClinicalTrials.gov ID
- NCT04286438
- Acronym / sponsor ID
- REVERSE-IT / PB2452-PT-CL-0004
- Conditions
- Hemorrhage, Urgent Surgery, Invasive Procedure
- Keywords
- Bleeding
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 226 participants (actual)
- Lead sponsor
- SFJ Pharmaceuticals, Inc.Industry (pharma, biotech, devices)
- Study start
- 15 Jul 2020 (actual)
- Primary completion
- 9 Sep 2024 (actual)
- Study completion
- 9 Sep 2024 (actual)
- First posted
- 27 Feb 2020 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
This is a multi-center, open-label, prospective single-arm study of reversal of the antiplatelet effects of ticagrelor with bentracimab (PB2452) in patients who present with uncontrolled major or life-threatening bleeding or who require urgent surgery or invasive procedure.
At least 200 patients will be enrolled from approximately 200 centers in North America, Europe, and Asia-Pacific regions, including mainland China. Patients with reported use of ticagrelor within the prior 3 days who require urgent ticagrelor reversal will be eligible for enrollment. These populations will be enrolled based on separate inclusion criteria.
Detailed description
The study will consist of a Screening/Pre-treatment period, an on-site assignment to study treatment and administration, a Follow-up visit on (Day 3+1 and Day 7±1), a Final Follow-up visit (Day 35±3) and a Follow-up visit for intracranial hemorrhage (ICH) only patients (Day 90±10). Infusion of PB2452 will be initiated on Day 1 and will continue for approximately 16 hours for a total of 18 g.
On Day 1, subjects who meet all the inclusion criteria and none of the exclusion criteria will receive an intravenous (IV) infusion comprised of an initial IV bolus of 6 grams (g) infused over 10 minutes for rapid reversal, followed immediately by a 6g IV loading infusion over 4 hours and then a 6 g IV maintenance infusion over 12 hours. This bentracimab (PB2452) regimen is expected to provide immediate reversal of the antiplatelet effects of ticagrelor within 5 minutes of the initiation of infusion that is sustained for 20-24 hours.
In subjects with potential drug interaction from recent concomitant use of moderate or strong CYP3A inhibitors with ticagrelor, an alternative regimen may be used comprising administration of 36 g over an active treatment period of 24 hours and 10 min. (This alternative regimen will be an initial 12 g bolus infusion over 10 minutes, followed immediately by a loading infusion of 12 g over 6 hours which will then be followed by a maintenance regimen of 12 g infused over 18 hours for a total infusion of 36 grams over 24 hours and 10 minutes).
In patients presenting with intracranial hemorrhage (ICH), brain imaging within 2 hours of initiation of study drug and at least one follow-up brain imaging performed 12-24 hours post completion of PB2452 will be required to support adjudication of hemostasis.
All subjects may be discharged from the clinical site between Days 3 and 7 inclusive and will return for a Follow-up visit on Day 7, if already discharged, and on Day 35 (± 3 days). All ICH patients must complete End of Study (EOS) Day 35±3 (Visit 5). ICH patients that agree to participate in the ICH-only-90-day-follow-up visit will have an additional visit on Day 90±10 (Visit 6).
Study design
- Primary purpose
- Treatment
- Allocation
- Not applicable
- Intervention model
- Single group
- Masking
- None (open label)
- Number of arms
- 1
| Arm | Type | Receives |
|---|---|---|
| Bentracimab (PB2452) Infusion - Open Label Active Drug | Experimental | Drug: Bentracimab (PB2452) InfusionBentracimab (PB2452) 18 g Intravenous Infusion over a 16 hour duration. For patients with uncontrolled major or life-threatening bleeding or in need of urgent surgery or invasive procedure. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (12 listed)
- Patients will be eligible for inclusion into the study if they meet all of the following criteria:
- 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.
- History or documentation of ticagrelor intake within the prior 3 days
- 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:
Key exclusion criteria (6 listed)
- Known sensitivity or contraindication to PB2452 or any of its excipients
- 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
- Patients expected to be clinically unsalvageable, such as, patients with end-stage cancer or patients with overwhelming sepsis
- 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
- 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
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| Bentracimab (PB2452) InfusionBentracimab (PB2452) 18 g Intravenous Infusion over a 16 hour duration. In subjects with potential drug interaction from recent concomitant use of moderate or strong CYP3A inhibitors with ticagrelor, the active treatment period may be 24 hours and 10 min if receiving the 36g infusion. In patients presenting with intracranial hemorrhage (ICH), brain imaging within 2 hours of initiation of study drug and at least one follow-up brain imaging performed 12-24 hours post completion of PB2452. | Drug | Bentracimab (PB2452) Infusion - Open Label Active Drug |
Primary outcome
Reversal - Platelet Reactivity Units (PRU)
Time frame: 4 hours post-initiation of infusion
Minimum % inhibition of PRU within 4 hours of the initiation of study drug as assessed by VerifyNow™ PRUTest™ platelet function assay
Hemostasis - Uncontrolled major of life-threatening bleeding - Achievement
Time frame: 4 hours post-initiation of infusion
Achievement of effective (graded as good or excellent) hemostasis after initiation of PB2452 infusion will be assessed using prespecified criteria for effective hemostasis for visible and non-visible major bleeding [Scale (from best to worst) measured as: Excellent, Good, Poor/None]
Hemostasis - Urgent surgery or invasive procedure - Achievement
Time frame: 4 hours post-initiation of infusion
Achievement of effective hemostasis following initiation of PB2452 infusion will be centrally adjudicated using prespecified criteria for effective hemostasis derived from the Global Use of Strategies to Open Occluded Coronary Arteries (GUSTO) clinical bleeding scale [GUSTO scale (from best to worst): Effective (no bleeding, mild bleeding or moderate bleeding) or Not effective (severe bleeding)]
12 secondary outcomes
Minimum % inhibition of Platelet Reactivity Index (PRI) (VASP)
Time frame: 4 hours post-initiation of infusion
Maximum reversal of PRU assessed by VerifyNow™ PRUTest™
Time frame: 4 hours post-initiation of infusion
Maximum reversal of PRI assessed by VASP
Time frame: 4 hours post-initiation of infusion
Proportion of subjects achieving reversal of platelet inhibition of ticagrelor using PRU and PRI - 60%
Time frame: Any time point between infusion initiation and Day 3 (Pre-dose, 5-10 minutes, 30+5 minutes, 1+0.25 hours, 4+0.25 hours, 12+0.5 hours, 24+1 hours, and Day 3)
Proportion of subjects achieving reversal of platelet inhibition of ticagrelor using PRU and PRI - 80%
Time frame: Any time point between infusion initiation and Day 3 (Pre-dose, 5-10 minutes, 30+5 minutes, 1+0.25 hours, 4+0.25 hours, 12+0.5 hours, 24+1 hours, and Day 3)
Proportion of subjects achieving reversal of platelet inhibition of ticagrelor using PRU and PRI - 100%
Time frame: Any time point between infusion initiation and Day 3 (Pre-dose, 5-10 minutes, 30+5 minutes, 1+0.25 hours, 4+0.25 hours, 12+0.5 hours, 24+1 hours, and Day 3)
Duration of at least 60% reversal by PRU and PRI
Time frame: Any time point between infusion initiation and Day 3 (Pre-dose, 5-10 minutes, 30+5 minutes, 1+0.25 hours, 4+0.25 hours, 12+0.5 hours, 24+1 hours, and Day 3)
Duration of at least 80% reversal by PRU and PRI
Time frame: Any time point between infusion initiation and Day 3 (Pre-dose, 5-10 minutes, 30+5 minutes, 1+0.25 hours, 4+0.25 hours, 12+0.5 hours, 24+1 hours, and Day 3)
Duration of at least 100% reversal by PRU and PRI
Time frame: Any time point between infusion initiation and Day 3 (Pre-dose, 5-10 minutes, 30+5 minutes, 1+0.25 hours, 4+0.25 hours, 12+0.5 hours, 24+1 hours, and Day 3)
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)
Time frame: [Time Frame: Pre-dose, Day 35 and Day 90]
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)
Time frame: [Time Frame: Pre-dose, Day 35 and Day 90]
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)
Time frame: [Time Frame: Pre-dose, Day 35 and Day 90]
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 21 Oct 2024.
- Derived from this study: PubMed 38319214Bhatt DL, Pollack CV, Mazer CD, Angiolillo DJ, Steg PG, James SK, Weitz JI, Ramnath R, Arnold SE, Mays MC, Umstead BR, White B, Hickey LL, Jennings LK, Curry BJ, Lee JS, Verma S. Bentracimab for Ticagrelor Reversal in Patients Undergoing Urgent Surgery. NEJM Evid. 2022 Mar;1(3):EVIDoa2100047. doi: 10.1056/EVIDoa2100047. Epub 2021 Dec 1.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Deepak Bhatt, MD, MPH study chair
Brigham and Women's Hospital, Division of Cardiovascular Medicine
68 sites in 13 countries: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Bentracimab (PB2452) Infusion in people with Hemorrhage and Urgent Surgery, run by SFJ Pharmaceuticals, Inc. at 68 sites in 13 countries.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 12 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 21 Oct 2024. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 68 sites in China, United States, Canada, Belgium, Spain and 8 more countries. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Reversal - Platelet Reactivity Units (PRU) (time frame: 4 hours post-initiation of infusion). The study lists 3 primary outcomes in all. It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT04286438, which also lists 1 linked publication.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 21 Oct 2024.