Clinical trial NCT06815471: CRF2 Agonist for the Treatment of Worsening Heart Failure
Official title: Corticotrophin Releasing Factor 2 for the Treatment of Worsening Heart Failure (WHF) - the CRAFT-WHF Study
Study type: INTERVENTIONAL
Overall status: NOT_YET_RECRUITING
Phase: PHASE2
Conditions: Worsening Heart Failure
Keywords: COR-1167
Hospitalised heart failure
WHF
Lead sponsor: Corteria Pharmaceuticals
Sponsor class: INDUSTRY
Collaborators: name: Worldwide Clinical Trials
First posted: 2025-02-07
Enrollment: 300
Sex: ALL
Minimum age (years): 18
Maximum age (years): 85
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: RANDOMIZED
Intervention model: PARALLEL
Primary purpose: TREATMENT

Brief summary: This study assesses the effects of the investigational drug COR-1167 in subjects hospitalised due to worsening of heart failure (HF)

Detailed description: This is a phase 2b, randomized, double-blind, placebo-controlled study designed to assess the dose-dependent effects of 3 doses of the corticotropin-releasing factor type 2 (CRF2) peptide agonist, COR-1167, in subjects with WHF, defined as subjects requiring urgent administration of intravenous (i.v.) diuretics due to worsening of signs and symptoms of heart failure (HF) associated with volume overload

Eligibility criteria: Inclusion Criteria:

* Signed written informed consent
* Heart failure hospitalization (HFH) during previous 12 months
* Prescribed an oral loop diuretic for at least 1 month preceding the index event
* NT-proBNP ≥1,000 pg/mL or BNP ≥250 pg/mL
* Requires treatment with i.v. diuretics for volume overload
* At least 1 risk factor for diuretic resistance
* Admitted to the hospital not more than 48 hours prior to randomization

Exclusion Criteria:

* Index event primarily triggered by an acute event (e.g. AMI, PE, arrhythmia)
* Requirement for i.v. inotropic therapy or i.v. vasodilators, mechanical ventilation, high-flow oxygen therapy, or NIV
* Requirement for, or planned use of LVADs, IABP, or any type of MCS
* History of solid organ transplant or active on a transplant list
* SBP \<100 mmHg
* eGFR \< 20 mL/min/1.73 m2
* CABG, PCI, implantation of CRT, heart valve procedure or any cardiac surgery within 1 month prior to screening or planned during the study
* Severe stenotic cardiac valvular disease
* Severe chronic pulmonary disease requiring chronic steroid therapy or chronic oxygen therapy (\> 2 L/min)
* Uncorrected severe hyperthyroidism or hypothyroidism
* Severe restrictive, obstructive, or infiltrative cardiomyopathy
* Body weight \< 70 kg
* Use of any investigational drug(s) within 5 half-lives of screening
* At high risk of death (defined as life expectancy ≤1 year) from causes other than heart failure or any disease that, in the opinion of the Investigator, will preclude their safe participation in this study, and will make implementation of the protocol or interpretation of the study results difficult
* Presence of any other conditions (e.g. geographic, social) actual or anticipated, that the Investigator feels would restrict or limit the subject's participation or compliance with all study procedures Subject is the Investigator or any Subinvestigator, research assistant, pharmacist, study coordinator, other staff or relative thereof directly involved in the conduct of the study

Primary outcomes:
measure: Natriuresis
timeFrame: 24 hours
measure: Body weight
timeFrame: 7 days
measure: NT-proBNP
timeFrame: 7 days
measure: Kansas City Cardiomyopathy Questionnaire (KCCQ)-Total Symptom Score (TSS)
timeFrame: 28 days
measure: Left Atrial Volume index (LAVi)
timeFrame: 2 days
Secondary outcomes:
Other outcomes:
Locations:
Study officials:
affiliation: Yale University
name: Jeffrey Testani, MD
role: STUDY_CHAIR
References:
citation: Rademaker MT, Charles CJ, Ellmers LJ, Lewis LK, Nicholls MG, Richards AM. Prolonged urocortin 2 administration in experimental heart failure: sustained hemodynamic, endocrine, and renal effects. Hypertension. 2011 Jun;57(6):1136-44. doi: 10.1161/HYPERTENSIONAHA.111.173203. Epub 2011 May 2.
citation: Rademaker MT, Charles CJ, Nicholls MG, Richards AM. Urocortin 2 inhibits furosemide-induced activation of renin and enhances renal function and diuretic responsiveness in experimental heart failure. Circ Heart Fail. 2009 Nov;2(6):532-40. doi: 10.1161/CIRCHEARTFAILURE.109.861336. Epub 2009 Sep 22.
citation: Ponikowski P, Voors AA, Anker SD, Bueno H, Cleland JG, Coats AJ, Falk V, Gonzalez-Juanatey JR, Harjola VP, Jankowska EA, Jessup M, Linde C, Nihoyannopoulos P, Parissis JT, Pieske B, Riley JP, Rosano GM, Ruilope LM, Ruschitzka F, Rutten FH, van der Meer P; Authors/Task Force Members; Document Reviewers. 2016 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure: The Task Force for the diagnosis and treatment of acute and chronic heart failure of the European Society of Cardiology (ESC). Developed with the special contribution of the Heart Failure Association (HFA) of the ESC. Eur J Heart Fail. 2016 Aug;18(8):891-975. doi: 10.1002/ejhf.592. Epub 2016 May 20. No abstract available.
citation: Chan WY, Frampton CM, Crozier IG, Troughton RW, Richards AM. Urocortin-2 infusion in acute decompensated heart failure: findings from the UNICORN study (urocortin-2 in the treatment of acute heart failure as an adjunct over conventional therapy). JACC Heart Fail. 2013 Oct;1(5):433-41. doi: 10.1016/j.jchf.2013.07.003. Epub 2013 Sep 11.
citation: Rubio-Gracia J, Demissei BG, Ter Maaten JM, Cleland JG, O'Connor CM, Metra M, Ponikowski P, Teerlink JR, Cotter G, Davison BA, Givertz MM, Bloomfield DM, Dittrich H, Damman K, Perez-Calvo JI, Voors AA. Prevalence, predictors and clinical outcome of residual congestion in acute decompensated heart failure. Int J Cardiol. 2018 May 1;258:185-191. doi: 10.1016/j.ijcard.2018.01.067.
citation: Go AS, Mozaffarian D, Roger VL, Benjamin EJ, Berry JD, Blaha MJ, Dai S, Ford ES, Fox CS, Franco S, Fullerton HJ, Gillespie C, Hailpern SM, Heit JA, Howard VJ, Huffman MD, Judd SE, Kissela BM, Kittner SJ, Lackland DT, Lichtman JH, Lisabeth LD, Mackey RH, Magid DJ, Marcus GM, Marelli A, Matchar DB, McGuire DK, Mohler ER 3rd, Moy CS, Mussolino ME, Neumar RW, Nichol G, Pandey DK, Paynter NP, Reeves MJ, Sorlie PD, Stein J, Towfighi A, Turan TN, Virani SS, Wong ND, Woo D, Turner MB; American Heart Association Statistics Committee and Stroke Statistics Subcommittee. Executive summary: heart disease and stroke statistics--2014 update: a report from the American Heart Association. Circulation. 2014 Jan 21;129(3):399-410. doi: 10.1161/01.cir.0000442015.53336.12. No abstract available.