Ciraparantag (aripazine) / Norgine, Azurity Pharma - LARVOL DELTA

PK and PD of Single, Escalating Doses of PER977 Following Enoxaparin (clinicaltrials.gov) - P1/2 | N=40 | Completed | Sponsor: Perosphere, Inc. | Active, not recruiting ➔ Completed

Trial completion

PK and PD of Single, Escalating Doses of PER977 Following Enoxaparin (clinicaltrials.gov) - P1/2 | N=40 | Active, not recruiting | Sponsor: Perosphere, Inc.

New P1/2 trial

Nanotechnology - Driven Innovations in Anticoagulant Delivery and Antidote Development for Hemostasis Regulation. (PubMed, Cardiovasc Hematol Disord Drug Targets) - "This review highlights the novelty of integrating nanotechnology-based delivery systems with targeted antidote strategies. Such convergence offers a patient-centred, safer, and more effective framework for anticoagulant therapy, while underscoring the need for future research in clinical translation, cost-effectiveness, and long-term safety."

Journal • Cardiovascular • Venous Thromboembolism

From empirical hemostasis to precision reversal: clinical challenges, technological innovations, and individualized strategies in anticoagulant-associated bleeding. (PubMed, Front Cardiovasc Med) - "While specific reversal agents (e.g., idarucizumab, andexanet alfa) have inaugurated an era of targeted precision reversal through high-affinity molecular neutralization, their widespread application is frequently hampered by exorbitant pharmacoeconomic costs, limited accessibility, and latent prothrombotic "off-target" effects (e.g., TFPI inhibition)...To circumvent existing limitations, current technological trajectories are pivoting towards the rational design of broad-spectrum synthetic molecules (e.g., ciraparantag) and highly programmable nucleic acid aptamer systems...We propose a multidimensional framework driven by point-of-care (POC) viscoelastic testing, algorithmic clinical decision support systems, and sequential therapy pathways managed by multidisciplinary "Code Bleed" teams. Future research must urgently prioritize large-scale, head-to-head randomized trials focused on patient-centered hard endpoints, ultimately refining evidence-based..."

Journal • Review • Cardiovascular • Hematological Disorders

Anticoagulation Stewardship Program in the DOAC Era. (PubMed, J Clin Med) - "Recent regulatory changes have altered the reversal landscape, notably with the withdrawal of andexanet alfa from the U.S. market... Idarucizumab remains the only FDA-approved specific antidote for dabigatran...Ciraparantag, a universal reversal agent, is currently in Phase III development...Success in DOAC-associated bleeding management now depends on optimizing PCC-based strategies, integrating systematic stewardship approaches, and preparing for emerging universal antidotes. Institutions must urgently update algorithms, ensure PCC availability, and monitor outcomes in this new therapeutic environment."

Journal • Review

Factor IIa Inhibitors: Mechanisms, Clinical Complications, and Advances in Reversal Strategies (THSNA 2026) - "Direct thrombin inhibitors, such as dabigatran, argatroban, and bivalirudin, provide targeted anticoagulation across a wide range of cardiovascular and hematologic settings...Special focus was placed on specific reversal agents such as idarucizumab, the use of four-factor prothrombin complex concentrates, and investigational options such as Ciraparantag...Idarucizumab, a monoclonal antibody fragment with strong binding affinity for dabigatran, is the only United States Food and Drug Administration-approved reversal agent for any direct thrombin inhibitor and rapidly restores clotting parameters...Continued clinical research will determine its safety, efficacy, and overall impact on the future of anticoagulation management. No part of this publication may be reproduced, distributed, or transmitted in any form or by any means, including photocopying, recording, or other electronic or mechanical methods, without the prior written permission of the author."

Clinical • Atrial Fibrillation • Cardiovascular • Hematological Disorders • Thrombocytopenia • Venous Thromboembolism

Efficient Small-Molecule Reversal Agents for Anticoagulant Fondaparinux. (PubMed, ACS Pharmacol Transl Sci) - "In an in vitro enzymatic assay related to blood coagulation, the spermine derivatives show potent activity as fondaparinux antidotes, with higher activity than ciraparantag (a small molecule in the clinical phase as an anticoagulant antidote) and much higher activity than protamine, the only approved antidote for unfractioned heparin but inefficient against fondaparinux. Mechanistic studies show that both small molecules strongly bind fondaparinux in buffered water, as detected by fluorescence and NMR spectroscopy and confirmed by molecular dynamics simulations. Thus, these spermine derivatives are promising reversal agents against heparinoid anticoagulants with a wide range of molecular weights, overcoming the drawbacks of those antidotes based on biomacromolecules."

Journal

Study of Ciraparantag for Reversal of Anticoagulation Induced by Edoxaban, Apixaban or Rivaroxaban in Healthy Adults (clinicaltrials.gov) - P2 | N=41 | Terminated | Sponsor: AMAG Pharmaceuticals, Inc. | N=108 ➔ 41 | Recruiting ➔ Terminated; Sponsor decision unrelated to safety

Enrollment change • Trial termination

Correction of the effect of direct oral and parenteral anticoagulants in hemorrhagic stroke (PubMed, Zh Vopr Neirokhir Im N N Burdenko) - "Early hemostatic therapy and reversal of anticoagulant effects in patients with hemorrhagic stroke significantly reduce the risk of adverse outcomes. This problem is being studied. Regular literature review with creation of updated clinical guidelines is needed."

Journal • Review • Cardiovascular • Cerebral Hemorrhage • Hematological Disorders • Thrombocytopenia

Study of Ciraparantag for Reversal of Anticoagulation Induced by Edoxaban, Apixaban or Rivaroxaban in Healthy Adults (clinicaltrials.gov) - P2 | N=108 | Recruiting | Sponsor: Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc. | Trial completion date: Dec 2023 ➔ Dec 2024 | Trial primary completion date: Dec 2023 ➔ Dec 2024

Trial completion date • Trial primary completion date

Is there a role for the laboratory monitoring in the management of specific antidotes of direct oral anticoagulants? (PubMed, Thromb Res) - "Idarucizumab is commercialized as a specific antidote to dabigatran while andexanet alfa has gained the Food and Drug Administration and the European Medicines Agency approval as an oral anti-factor Xa inhibitors antidote...However, these tests might be inconclusive after some antidote administration, namely andexanet alfa and ciraparantag. The benefit of laboratory monitoring following DOAC reversal remains unclear. Here, we sought to provide an overview of the key studies evaluating the safety and efficacy of DOAC reversal using the most developed/commercialized specific antidotes, to discuss the potential role of the laboratory monitoring in the management of patients receiving DOAC specific antidotes and to highlight the areas that deserve further investigations in order to establish the exact role of laboratory monitoring in the appropriate management of DOAC specific antidotes."

Journal • Review

Latest advances in the reversal strategies for direct oral anticoagulants. (PubMed, Fundam Clin Pharmacol) - "With the validation of specific and nonspecific antidotes, DOACs could supplant traditional oral anticoagulants. This progress represents a significant advancement in anticoagulation therapy. However, ongoing research is crucial to address remaining safety concerns of the specific reversion agents of DOACs in clinical practice."

Journal • Review • Cardiovascular • Hematological Disorders • Thrombosis

Study of Ciraparantag for Reversal of Anticoagulation Induced by Edoxaban, Apixaban or Rivaroxaban in Healthy Adults (clinicaltrials.gov) - P2 | N=108 | Recruiting | Sponsor: Perosphere Pharmaceuticals Inc, a wholly owned subsidiary of AMAG Pharmaceuticals, Inc. | Trial completion date: Dec 2022 ➔ Dec 2023 | Trial primary completion date: Dec 2022 ➔ Dec 2023

Trial completion date • Trial primary completion date

Comparison of Cardiovascular and Respiratory Toxicity of Heparin Antidotes: Protamine Sulfate, PER977 and Heparin-Binding Copolymer (HBC) (ISTH 2023) - "HBC with dose escalation most significantly reduced blood pressure and increased perfusion of paw vessels, which was accompanied by complement system activation and secretion of NO and angiotensin 1-7. We observed the respiratory disturbances and increased angiotensin II and thromboxane B2 production after protamine and HBC infusion. Protamine-induced hypotension and vasodilatation were accompanied by the release of prostacyclin metabolite and angiotensin 1-7 (Figure 1A-G)."

Cardiovascular • Hypotension

Direct oral anticoagulants improve podocyte health and reverse hypercoagulopathy in an experimental model of glomerular disease (ISTH 2023) - "IVC ligation experiments were performed on day 10 to investigate in vivo effects of DOAC treatment with or without ciraparantag, an investigational DOAC antidote. Both DOACs significantly improved proteinuria, decreased podocyte injury, and reduced ETP. DOAC-Stop reversed 30% of the dabigatran effect on ETP, suggesting that 70% of the effect was due to its antiproteinuric effect. Similarly, rivaroxaban had both a direct anticoagulant and an indirect antiproteinuric effect on ETP (49% and 51% of total effect, respectively)."

Cardiovascular • Glomerulonephritis • Hematological Disorders • Infectious Disease • Nephrology • Renal Disease • Thrombosis

"Translation, Ciraparantag is coming soon!" (,@puppy_chow1)

"👍🏻👍🏻 Also Ciraparantag - Universal antidote 😎 (against Heparin, LMWH and DOACs) - acts by formation of hydrogen bonds" (,@DigambarPanchal)

When and How to Use Reversal Agents for Direct Oral Anticoagulants? (PubMed, Curr Cardiol Rep) - "Specific (idarucizumab for dabigatran and andexanet alfa for direct factor Xa inhibitors) and non-specific (prothrombin complex concentrates) reversal agents are effective in neutralizing the anticoagulant effect of DOACs. New investigational antidotes such as ciraparantag and VMX-C001 offer an alternative to andexanet alfa in reversing the anticoagulant activity of direct oral factor Xa inhibitors, but more clinical data are needed before they could be licensed for use. Specific reversal agents are recommended for use in clinical situations within their licensed indications (i.e.: reversal of DOACs in patients with severe uncontrolled or life-threatening bleeding or in need of emergency surgery or other invasive procedures), while non-specific reversal agents may be used when specific antidotes are not available or indicated."

Journal • Review

Anticoagulation for Atrial Fibrillation: A Review of Current Literature and Views. (PubMed, Cardiol Rev) - "Since early 2010s, direct oral anticoagulants (DOACs) including dabigatran, rivaroxaban, apixaban, and edoxaban have been introduced and approved for anticoagulation of atrial fibrillation. One major concern and disadvantage for DOACs was lack of reversal agents, which have largely been ameliorated by the approval of Idarucizumab for dabigatran and Andexanet alfa for both apixaban and rivaroxaban, with Ciraparantag as a universal reversal agent for all DOACs undergoing Fast-Track Review from FDA. In this article, we will be providing a broad review of anticoagulation for atrial fibrillation with a focus on risk stratification schemes and anticoagulation agents (warfarin, aspirin, DOACs) including special clinical considerations."

Journal • Review • Atrial Fibrillation • Cardiovascular • Cerebral Hemorrhage • CNS Disorders • Hematological Disorders • Immunology • Ischemic stroke • Ventricular Tachycardia

Reversal agents for severe bleeding associated with direct oral anticoagulants (PubMed, G Ital Cardiol (Rome)) - "Idarucizumab has been approved for dabigatran reversal and andexanet alfa was recently granted approval for the reversal of apixaban or rivaroxaban in patients with life-threatening or uncontrolled bleeding events. Other reversal agents (e.g. ciraparantag for heparins and DOACs) are under development. Non-specific prohemostatic agents (e.g. prothrombin complex concentrate) can counteract the anticoagulant action of DOACs in emergency situations, when specific reversal agents are unavailable. However, specific reversal agents are efficacious and safe and should be preferred when available."

Journal

Reversal of direct oral anticoagulants: what about new treatments available? (PubMed, Rev Med Suisse) - "Recently, we have seen the emergence of specific antidotes to DOAC, such as idarucizumab and andexanet alfa, effective on anti-II and anti-Xa DOAC respectively. These new molecules have shown excellent biological efficacy, hence supporting their use in clinical practice, however they are not routinely used, mainly due to limited availability and high cost. Ciraparantag, an antagonist of DOAC and heparins currently in phase III trials, could become a key molecule in the future considering encouraging preliminary results."

Journal

A short review of ciraparantag in perspective of the currently available anticoagulant reversal agents. (PubMed, Drug Discov Today) - "Ciraparantag, a synthetic small molecule that inactivates heparins and DOAC, is a promising new reversal agent that has been investigated in phase 2 trials. In this short review we provide an overview of the preclinical and clinical evidence of ciraparantag, and compare strengths and weaknesses of ciraparantag and the currently available anticoagulant reversal strategies."

Journal • Review

"The next DOAC reversal agent? Ciraparantag!" (,@Bloodman)

"Ciraparantag as a potential universal anticoagulant reversal agent - Editorial https://t.co/ADLNNO4thY" (,@JerroldLevy)

"Ciraparantag reverses the anticoagulant activity of apixaban and rivaroxaban in healthy elderly subjects https://t.co/oxOz1za2WG" (,@JerroldLevy)

Clinical