A Study to Investigate the Effect of Triferic Plus Heparin Infusion Compared to Heparin Alone on Coagulation Parameters in Hemodialysis Patients

Study Overview
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Brief Summary
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This study will investigate the effect of co-administration of Triferic and heparin on the ability to maintain circuit anti-coagulation and iron delivery when compared to control conditions when each treatment is administered via separate routes.

Official Title
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A Randomized 3 Period Crossover Study to Investigate the Effect of Triferic Plus Heparin Infusion Compared to Heparin Alone on Coagulation Parameters in Hemodialysis Patients

Conditions
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End Stage Renal Disease

Intervention / Treatment
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* Drug: Triferic
* Drug: Heparin


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Adult hemodialysis patients ≥18 years of age. Signed informed consent to participate in the study. Stable on hemodialysis prescription for ≥3 months. Hemoglobin concentration >9.5 g/dL. Serum TSAT ≥20%. Able to receive continuous heparin infusion as their anticoagulation protocol. Receiving hemodialysis via AV (arteriovenous) fistula or graft. Able to receive hemodialysis for 4 hours at each session over the duration of the treatment periods. Exclusion Criteria: Active bleeding disorder (GI, skin, nasal…) Receiving hemodialysis via catheter. Receiving heparin free dialysis. Receiving low molecular weight heparin as sole anti-coagulation for dialysis. Receiving IV iron within 2 weeks of the first on-study hemodialysis treatment. Receiving oral anti-coagulants or anti-platelet agents. Any other condition, that in the opinion of the investigator would not allow completion of the 3 hemodialysis treatments in the study.

Ages Eligible for Study
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Minimum Age: 18 Years

Sexes Eligible for Study
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All

Accepts Healthy Volunteers
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No

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Treatment
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: Triferic post-dialyzer; UFH via continuous infusion<br>Patients will receive Triferic 6.75 mg IV over 3 hours into the post-dialyzer blood line (or drip chamber) administered by an infusion pump. Anti-coagulation will be provided by a bolus of heparin administered into the venous return line immediately prior to the initiation of hemodialysis followed by a continuous infusion of heparin using the on-machine infusion pump. The infusion of heparin to be stopped at hour 3 of hemodialysis. | Drug: Triferic<br>* Triferic (ferric pyrophosphate citrate, FPC), an iron-replacement product, is an iron complex in which iron(III) is bound to pyrophosphate and citrate.<br>* Other names: FPC;Drug: Heparin<br>* Unfractionated heparin (UFH): a common anticoagulant used during hemodialysis treatments.<br>* Other names: UFH;|
| Experimental: UFH and Triferic admixture<br>Patients will receive Triferic 6.75 mg IV plus the appropriate volume of unfractionated heparin for continuous infusion over 3 hours into the pre-dialyzer heparin line. This mixture will be administered by the on-machine syringe infusion pump for continuous infusion. Anti-coagulation will be provided by a bolus of heparin administered into the venous return line immediately prior to the initiation of hemodialysis followed by a continuous infusion of Triferic + heparin. The infusion of Triferic + heparin will be stopped at hour 3 of hemodialysis. | Drug: Triferic<br>* Triferic (ferric pyrophosphate citrate, FPC), an iron-replacement product, is an iron complex in which iron(III) is bound to pyrophosphate and citrate.<br>* Other names: FPC;Drug: Heparin<br>* Unfractionated heparin (UFH): a common anticoagulant used during hemodialysis treatments.<br>* Other names: UFH;|
| Experimental: UFH via continuous infusion pre-dialyzer<br>Patients will receive no Triferic. Anti-coagulation will be provided by a bolus of heparin administered into the venous return line immediately prior to the initiation of hemodialysis followed by a continuous infusion of heparin via the on-machine syringe pump. The infusion of heparin to be stopped at hour 3 of hemodialysis | Drug: Heparin<br>* Unfractionated heparin (UFH): a common anticoagulant used during hemodialysis treatments.<br>* Other names: UFH;|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-Xa Activity as Measured by the AUC (Area Under the Curve) 0-t |  | 8 hours | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Anti-Xa Activity as Measured by the AUC (Area Under the Curve) 0-4 Hours |  | 4 hours | 
| aPTT (Activated Partial Thromboplastin Time) as Measured by the AUC (Area Under the Curve) 0-4 Hours |  | 4 hours | 
| TT (Thrombin Time) as Measured by the AUC (Area Under the Curve) 0-4 Hours |  | 4 hours | 
| Iron Profile as Measured by the sFe Cmax (Peak Serum Iron Concentration) |  | 8 hours | 
| Iron Profile as Measured by the AUC (Area Under the Curve) 0-t |  | 8 hours |