Prevention of Intradialytic Hypotension by Inhibiting Bradykinin B2 Receptor

NCT05834777 | Recruiting Phase 3 DMC FDA Drug

• 1 other identifier: 222301
• Study Type: interventional
• Target: 26
• Locations: 1 country
• Sites: 1

Brief Summary

Currently, there is no medication available to adequately treat patients undergoing hemodialysis who are suffering from intradialytic hypotension (IDH). Medical interventions such as Trendelenburg positioning, saline bolus administration, reduction of ultrafiltration rate, interruption of the hemodialysis, and other medical treatments are the methods of choice to treat the hypotensive condition of these patients and thus to maintain the systolic blood pressure. Patients suffering from IDH have a higher reported mortality rate due to the given stress on their cardiovascular system. New treatments, therefore, would give clinicians an additional alternative to current existing approaches and might help patients to maintain their blood pressure during hemodialysis. The main objective of the study is to evaluate the efficacy of icatibant in the prevention of systolic blood pressure (SBP) drop in patients on hemodialysis suffering from recurrent IDH episodes during hemodialysis.

Conditions

Intradialytic Hypotension

Keywords

Hemodialysis; Intradialytic hypotension; Bradykinin; Kallikrein-Kinin System; Icatibant

Outcome Measures

Primary Outcomes (1)

• Blood pressure during hemodialysis

  Average systolic blood pressure

  0-8 weeks

Secondary Outcomes (2)

• Hypotension events

  0-8 week

• Symptomatology associated with hypotension

  0-8 weeks

Study Arms (2)

Icatibant

EXPERIMENTAL

153 mL 0.9% saline bag containing 30 mg icatibant acetate (10 mg/ml) IV at each dialysis treatment for four weeks (12 hemodialysis sessions)

Drug: Icatibant

Placebo

PLACEBO COMPARATOR

153 mL 0.9% saline bag IV at each dialysis treatment at each dialysis treatment for four weeks (12 hemodialysis sessions)

Drug: Placebo

Interventions

Icatibant DRUG

Icatibant will be administered with an infusion rate of 100µg/kg/h for 15 minutes before their hemodialysis session (pre-infusion) and 50µg/kg/h during their routine hemodialysis session (maintenance infusion).

Icatibant

Placebo DRUG

0.9% sodium chloride will be administered as the same rate as icatibant

Placebo

Eligibility Criteria

• Age: 18 Years - 80 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥ 18 to ≤ 80 years of age
• Patients with end-stage renal disease on hemodialysis (including hemodiafiltration) for at least 6 months, receiving 3 dialysis sessions per week and who are in a stable clinical condition per investigator's judgement
• Patients on hemodialysis with at least 6 IDH episodes during the last 8 weeks based on medical record assessment
• Pre-dialysis systolic blood pressure ≥ 110 and ≤ 170 mmHg assessed by two consecutive and averaged pre-HD blood pressure measurments
• Patients adequately hemodialyzed with a Kt/V ≥ 1.2
• Patients whose treatment regimen remained unchanged within 14 days prior to dosing (diet, medication, dry weight, treatment time, dialysate composition and temperature, dialysis shift, blood flow, and dialysate flow, vascular access)
• Female subjects \< 55 years of age to agree on effective contraception methods throughout the study period and who have a negative pregnancy test before initiating study activities
• Body weight ≤ 150 kg

You may not qualify if:

• Patients who have been hospitalized during the last 4 weeks before enrolment, except vascular access related hospitalization
• Patients with known clinically evident inflammatory or infectious disease per investigator's evaluation
• Severe anemia with a hemoglobin (Hb) \< 8.0 g/dL at screening
• Platelet count \< 50 x 109/L
• Hepatic disease associated with ALT \> 3x ULN, or total bilirubin \>2x ULN with direct bilirubin \> 20% of the total bilirubin level
• Known bleeding disorders e.g., von-Willebrand disease or Hemophilia A, B, C, etc.
• Recent (\<3 months before screening) thromboembolic event, e.g., acute coronary syndrome, stroke, or venous thrombosis embolism (except dialysis access thrombosis)
• Recent (\<3 months before screening) major surgery or scheduled major surgery during study participation
• Scheduled living donor renal transplant during study participation
• Persistent heart failure as classified by the New York Heart Association (NYHA) classification of 3 or higher
• Receiving antiplatelet therapy except daily ASA ≤ 150 mg/day
• Receiving anticoagulation in therapeutic doses, other than standard anticoagulation during the hemodialysis procedure
• Patients with significant pre-dialysis overload as defined by \> 5kg above dry weight estimated by bioimpedance spectroscopy
• Patient's life expectancy \< 6 months per investigator's judgement

Sponsors & Collaborators

• Vanderbilt University Medical Center: lead
• Pharvaris Netherlands B.V.: collaborator
• Renal Research Institute: collaborator

Study Sites (1)

Vanderbilt Fresenius

Nashville, Tennessee, 37212, United States

RECRUITING

MeSH Terms

Interventions

icatibant

Study Officials

• Jorge L Gamboa, MD/PhD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

• Peter Kotanko, MD, FASN

  Renal Research Institute

  PRINCIPAL INVESTIGATOR

• Talat A Ikizler, MD

  Vanderbilt University Medical Center

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Delia M Woods, BSN/MSL

CONTACT

615-327-7181; delia.woods@vumc.org

Study Design

• Study Type: interventional
• Phase: phase 3
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Masking Details: For the procedure of the cross-over main study, both participating sites will recruit patients that will be randomized through a centralized randomization key to ensuring an equally balanced allocation of patients to the respective cross-over groups (icatibant or placebo). All study personnel will be blinded except the IDS pharmacy.
• Purpose: HEALTH SERVICES RESEARCH
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Research Assistant Professor

Model Details: Randomized, placebo-controlled, cross-over study, with a pharmocokinetics evaluation phase. Study duration for main cross-over study: Approximately 60 days including screening evaluation activities.

Study Record Dates

• First Submitted: February 27, 2023
• First Posted: April 28, 2023
• Study Start: December 11, 2023
• Primary Completion (Estimated): July 1, 2026
• Study Completion (Estimated): November 1, 2026
• Last Updated: April 15, 2026

Record last verified: 2026-04

Data Sharing

• IPD Sharing: Will not share

Locations

US (1)