Hemodialysis ComplicationPhase 2SAFENCT04381234
Strategies for Asymmetrical Triacetate Dialyzer Heparin-Free Effective Hemodialysis
A Phase 2 study testing dialyzer, hemodialysis with citrate-containing dialysate and predilution hemodiafiltration in people with Hemodialysis Complication, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
Trial summary
Not all dialysis patients tolerate heparin anticoagulation. Heparin should be avoided in patients at high risk of bleeding. Strategies include saline infusion, citrate-containing dialysate, regional citrate anticoagulation and heparin-coated membranes. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Hemodialysis Complication
- What is being tested?
- dialyzer, hemodialysis with citrate-containing dialysate and predilution hemodiafiltration
- Type of treatment
- Medical device
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 20 participants
- Where
- 1 siteBelgium
- Study dates
- 6 Jan 2018to 5 May 2020
- Phase
- Phase 2
- 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 age 18 years, or over. No maximum age is defined.
- Providing signed and dated informed consent (ICF)
- Maintenance dialysis (> 3 months of hemodialysis)
- 'Standard' dialysis regimen (three dialysis sessions / week, dialysis duration 4 hours)
- Hemodynamic stability during 4 weeks preceding study period. Hemodynamic instability is defined as any episode of low blood pressure (asymptomatic or symptomatic requiring intervention (bolus fluid infusion, temporarily withholding or reducing ultrafiltration, preterm termination of dialysis session, resuscitation)
- Hemoglobin 9 - 12 g/dl.
Who cannot join
- Any known medical disorder favoring either bleeding or clotting (e.g. atypical hemolytic uremic syndrome (aHUS), antiphospholipid syndrome, idiopathic thrombocytopenic purpura (ITP), paroxysmal nocturnal hemoglobinuria (PNH))
- Treatment with a vitamin K antagonist
- Treatment with any one of the NOACs (apixaban, rivaroxaban, edoxaban, dabigatran)
- High risk of bleeding according to the criteria of Swartz (12).
- Patients with a known allergic reaction to asymmetric triacetate
- Pregnancy
Trial locations and contacts
1 site in 1 country.
About this study
Official title: Strategies for Asymmetrical Triacetate Dialyzer
Not all dialysis patients tolerate heparin anticoagulation. Heparin should be avoided in patients at high risk of bleeding. Strategies include saline infusion, citrate-containing dialysate, regional citrate anticoagulation and heparin-coated membranes. We recently studied the combination of a heparin-coated membrane and citrate-containing dialysate, with a success rate of 94% . Although this combination resulted in low rates of clotting, heparin-coated membranes are not ubiquitously available. The quest for easy to perform, safe and affordable heparin-free dialysis is on. Asymmetric cellulose triacetate (ATA) dialyzers have a low degree of platelet contact activation and might be an alternative to heparin-coated dialyzers.
This is a phase II pilot study in maintenance dialysis patients. Study design is a two-arm open-label cross-over study. In Arm 1, patients were dialyzed using a 1.9 m2 ATA membrane (Solacea™-19H, Nipro Corp., Japan) in combination with citrate (1 mM) containing dialysate. In Arm 2, patients were dialyzed with the same 1.9 m2 ATA membrane, in combination with high volume predilution hemodiafiltration. The primary endpoint was the success rate to complete 4 hours of hemodialysis without preterm clotting.
Read the detailed description
Anticoagulation is one of the supporting pillars of chronic hemodialysis (HD). The optimal anticoagulant regimen provides full anticoagulation of the extracorporeal circuit with minimal systemic effects and comes at an affordable cost. Unfractionated heparin (UFH) has been the standard of care for many years. In several countries, UFH has gradually been replaced by low molecular weight heparins (LMWH). LMWH are easy to use as they can be administered as a bolus injection and reduce membrane fibrin and platelet deposition. Both UFH and LMWH provide adequate anticoagulation of the extracorporeal circuit, at the price of systemic anticoagulation. Apart from bleeding, the administration of unfractionated heparins has also been associated with dyslipidemia, hypoaldosteronism and hyperkalemia, thrombopenia, osteoporosis, pruritus, and hypersensitivity reactions.
Several alternative anticoagulation regimens have been proposed including saline infusion, heparin coating of the dialyzer membrane as well as regional citrate anticoagulation. Regional citrate anticoagulation is performed by infusing citrate into the arterial line of the dialysis tubing to reduce ionized calcium concentrations in order to minimize propagation of the coagulation cascade. Ionized calcium concentrations are restored by calcium supplementation prior to reinfusion of the blood into the patient. The HepZero study suggested that regional citrate anticoagulation is superior to heparin-coated polyacrylonitrile dialyzers (AN69ST; Nephral 300ST, Gambro) and resulted in in significantly greater instantaneous urea nitrogen clearance. While generally safe and adequate, regional citrate anticoagulation requires additional actions during preparatory phase (preparation of citrate and calcium infusion pumps) as well as during the treatment (measurement of ionized calcium).
Recently, acetate-free citrate-containing dialysate concentrates were introduced into clinical practice. Besides the advantages of acetate-free dialysate, this provides a modest local anticoagulant effect inside the dialyzer. Citrate-containing dialysate allowed to reduce heparin dose while maintaining extracorporeal circuit patency and dialyzer clearance. Recently, citrate-containing dialysate and a heparin-coated dialyzer were combined. In one study, non-inferiority to regional citrate anticoagulation was demonstrated
The abovementioned studies demonstrate that hemodialysis without systemic heparinization is feasible. However, such procedures are more cumbersome, require more manpower, additional biochemical testing and/ or more expensive consumables. The aim of the current study is to test two different strategies for systemic heparin-free dialysis with an asymmetrical tri-acetate hemodialyzer.
Trial objectives To evaluate the feasability, safety and adequacy of systemic heparin-free dialysis using an asymmetrical tri-acetate dialyzer membrane, with or without the combination with citrate containing dialysate.
The main objective of the study is to test efficacy of the two study interventions to perform standard duration (i.e. 4 hours) hemodialysis without interruption due to clotting phenomena and without the use of heparin or low molecular weight heparins.
- Conditions
- Hemodialysis Complication
- Being tested
- dialyzer, hemodialysis with citrate-containing dialysate, predilution hemodiafiltration
- Keywords
- anticoagulation, clotting, hemodialysis, hemodiafiltration, citrate
- Medical subject headings
- Thrombosis
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
dialyzerDevice
Also called Solacea™-19H (Nipro Corp., Japan)
Asymmetric triacetate dialyzer
hemodialysis with citrate-containing dialysateCombination product
Also called Selectbag citrate (1mM citrate, Baxter)
acetate-free dialysate
predilution hemodiafiltrationOther
predilution hemodiafiltration
| Study group | Role | What they receive |
|---|---|---|
| ATA plus citrate | Experimental | 1.9 m2 ATA membrane (Solacea™-19H, Nipro Corp., Japan) in combination with citrate (1 mM) containing dialysate Receives: Device: dialyzer; Combination Product: hemodialysis with citrate-containing dialysate |
| ATA plus predilution hemodiafiltration | Active comparator | 1.9 m2 ATA membrane (Solacea™-19H, Nipro Corp., Japan), in combination with high volume predilution hemodiafiltration Receives: Device: dialyzer; Other: predilution hemodiafiltration |
What is being measured
The primary outcome is the main question the study is designed to answer.
clinical patency of the hemodialysis extracorporeal circuit
clotting of the extracorporeal circuit
Measured: 4 hours
Secondary outcomes (3)
Clotting of dialyser
Semi-quantitative clotting score
Measured: 4 hours
dialysis adequacy
single pool Kt/V
Measured: 4hours
Reduction ratio uremic retention solutes
ratio describing the change in serum concentration over the concentration at the beginning of the dialysis session
Measured: 4 hours
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted8 May 2020
- Study start6 Jan 2018
- Primary completion10 Mar 2019
- Study completion5 May 2020
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 Hemodialysis ComplicationStudies of the same condition, open and under way.
- More trials run by Universitaire Ziekenhuizen KU LeuvenThe sponsor's other registered studies.
- 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Model description
- open-label sequential cross-over study
- Masking
- None (open label)
- Enrolment
- 20 participants (actual)
Sponsor and investigators
- Lead sponsor
- Universitaire Ziekenhuizen KU Leuven
- Sponsor type
- University, hospital or other
- Collaborators
- NIPRO
- Responsible party
- Sponsor
- Investigators
- bjorn D Meijers, MD, PhD, Principal investigator, UZ Leuven
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04381234
- Sponsor's protocol ID
- S61285
- Acronym
- SAFE
- Status last verified
- May 2020
- First submitted
- 5 May 2020
- Last updated
- 21 May 2020
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Natale P, Palmer SC, Ruospo M, Longmuir H, Dodds B, Prasad R, Batt TJ, Jose MD, Strippoli GF. Anticoagulation for people receiving long-term haemodialysis. Cochrane Database Syst Rev. 2024 Jan 8;1(1):CD011858. doi: 10.1002/14651858.CD011858.pub2.
PubMed 38189593
Study at a glance
From the registry record, last updated by the sponsor on 21 May 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Strategies for Asymmetrical Triacetate Dialyzer
- ClinicalTrials.gov ID
- NCT04381234
- Acronym / sponsor ID
- SAFE / S61285
- Conditions
- Hemodialysis Complication
- Keywords
- anticoagulation, clotting, hemodialysis, hemodiafiltration, citrate
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 20 participants (actual)
- Lead sponsor
- Universitaire Ziekenhuizen KU LeuvenUniversity, hospital or other
- Collaborators
- NIPRO
- Study start
- 6 Jan 2018 (actual)
- Primary completion
- 10 Mar 2019 (actual)
- Study completion
- 5 May 2020 (actual)
- First posted
- 8 May 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.
Not all dialysis patients tolerate heparin anticoagulation. Heparin should be avoided in patients at high risk of bleeding. Strategies include saline infusion, citrate-containing dialysate, regional citrate anticoagulation and heparin-coated membranes. We recently studied the combination of a heparin-coated membrane and citrate-containing dialysate, with a success rate of 94% . Although this combination resulted in low rates of clotting, heparin-coated membranes are not ubiquitously available. The quest for easy to perform, safe and affordable heparin-free dialysis is on. Asymmetric cellulose triacetate (ATA) dialyzers have a low degree of platelet contact activation and might be an alternative to heparin-coated dialyzers.
This is a phase II pilot study in maintenance dialysis patients. Study design is a two-arm open-label cross-over study. In Arm 1, patients were dialyzed using a 1.9 m2 ATA membrane (Solacea™-19H, Nipro Corp., Japan) in combination with citrate (1 mM) containing dialysate. In Arm 2, patients were dialyzed with the same 1.9 m2 ATA membrane, in combination with high volume predilution hemodiafiltration. The primary endpoint was the success rate to complete 4 hours of hemodialysis without preterm clotting.
Detailed description
Anticoagulation is one of the supporting pillars of chronic hemodialysis (HD). The optimal anticoagulant regimen provides full anticoagulation of the extracorporeal circuit with minimal systemic effects and comes at an affordable cost. Unfractionated heparin (UFH) has been the standard of care for many years. In several countries, UFH has gradually been replaced by low molecular weight heparins (LMWH). LMWH are easy to use as they can be administered as a bolus injection and reduce membrane fibrin and platelet deposition. Both UFH and LMWH provide adequate anticoagulation of the extracorporeal circuit, at the price of systemic anticoagulation. Apart from bleeding, the administration of unfractionated heparins has also been associated with dyslipidemia, hypoaldosteronism and hyperkalemia, thrombopenia, osteoporosis, pruritus, and hypersensitivity reactions.
Several alternative anticoagulation regimens have been proposed including saline infusion, heparin coating of the dialyzer membrane as well as regional citrate anticoagulation. Regional citrate anticoagulation is performed by infusing citrate into the arterial line of the dialysis tubing to reduce ionized calcium concentrations in order to minimize propagation of the coagulation cascade. Ionized calcium concentrations are restored by calcium supplementation prior to reinfusion of the blood into the patient. The HepZero study suggested that regional citrate anticoagulation is superior to heparin-coated polyacrylonitrile dialyzers (AN69ST; Nephral 300ST, Gambro) and resulted in in significantly greater instantaneous urea nitrogen clearance. While generally safe and adequate, regional citrate anticoagulation requires additional actions during preparatory phase (preparation of citrate and calcium infusion pumps) as well as during the treatment (measurement of ionized calcium).
Recently, acetate-free citrate-containing dialysate concentrates were introduced into clinical practice. Besides the advantages of acetate-free dialysate, this provides a modest local anticoagulant effect inside the dialyzer. Citrate-containing dialysate allowed to reduce heparin dose while maintaining extracorporeal circuit patency and dialyzer clearance. Recently, citrate-containing dialysate and a heparin-coated dialyzer were combined. In one study, non-inferiority to regional citrate anticoagulation was demonstrated
The abovementioned studies demonstrate that hemodialysis without systemic heparinization is feasible. However, such procedures are more cumbersome, require more manpower, additional biochemical testing and/ or more expensive consumables. The aim of the current study is to test two different strategies for systemic heparin-free dialysis with an asymmetrical tri-acetate hemodialyzer.
Trial objectives To evaluate the feasability, safety and adequacy of systemic heparin-free dialysis using an asymmetrical tri-acetate dialyzer membrane, with or without the combination with citrate containing dialysate.
The main objective of the study is to test efficacy of the two study interventions to perform standard duration (i.e. 4 hours) hemodialysis without interruption due to clotting phenomena and without the use of heparin or low molecular weight heparins.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- open-label sequential cross-over study
| Arm | Type | Receives |
|---|---|---|
| ATA plus citrate | Experimental | Device: dialyzer, Combination Product: hemodialysis with citrate-containing dialysate1.9 m2 ATA membrane (Solacea™-19H, Nipro Corp., Japan) in combination with citrate (1 mM) containing dialysate |
| ATA plus predilution hemodiafiltration | Active comparator | Device: dialyzer, Other: predilution hemodiafiltration1.9 m2 ATA membrane (Solacea™-19H, Nipro Corp., Japan), in combination with high volume predilution hemodiafiltration |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (6 listed)
- Patients age 18 years, or over. No maximum age is defined.
- Providing signed and dated informed consent (ICF)
- Maintenance dialysis (> 3 months of hemodialysis)
- 'Standard' dialysis regimen (three dialysis sessions / week, dialysis duration 4 hours)
- Hemodynamic stability during 4 weeks preceding study period. Hemodynamic instability is defined as any episode of low blood pressure (asymptomatic or symptomatic requiring intervention (bolus fluid infusion, temporarily withholding or reducing ultrafiltration, preterm termination of dialysis session, resuscitation)
Key exclusion criteria (6 listed)
- Any known medical disorder favoring either bleeding or clotting (e.g. atypical hemolytic uremic syndrome (aHUS), antiphospholipid syndrome, idiopathic thrombocytopenic purpura (ITP), paroxysmal nocturnal hemoglobinuria (PNH))
- Treatment with a vitamin K antagonist
- Treatment with any one of the NOACs (apixaban, rivaroxaban, edoxaban, dabigatran)
- High risk of bleeding according to the criteria of Swartz (12).
- Patients with a known allergic reaction to asymmetric triacetate
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 |
|---|---|---|
| dialyzerAlso: Solacea™-19H (Nipro Corp., Japan)Asymmetric triacetate dialyzer | Device | ATA plus citrate, ATA plus predilution hemodiafiltration |
| hemodialysis with citrate-containing dialysateAlso: Selectbag citrate (1mM citrate, Baxter)acetate-free dialysate | Combination product | ATA plus citrate |
| predilution hemodiafiltrationpredilution hemodiafiltration | Other | ATA plus predilution hemodiafiltration |
Primary outcome
clinical patency of the hemodialysis extracorporeal circuit
Time frame: 4 hours
clotting of the extracorporeal circuit
3 secondary outcomes
Clotting of dialyser
Time frame: 4 hours
dialysis adequacy
Time frame: 4hours
Reduction ratio uremic retention solutes
Time frame: 4 hours
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 May 2020.
- Derived from this study: PubMed 38189593Natale P, Palmer SC, Ruospo M, Longmuir H, Dodds B, Prasad R, Batt TJ, Jose MD, Strippoli GF. Anticoagulation for people receiving long-term haemodialysis. Cochrane Database Syst Rev. 2024 Jan 8;1(1):CD011858. doi: 10.1002/14651858.CD011858.pub2.
- Individual participant dataSharing planned: No
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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.
bjorn D Meijers, MD, PhD principal investigator
UZ Leuven
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing dialyzer, hemodialysis with citrate-containing dialysate and predilution hemodiafiltration in people with Hemodialysis Complication, run by Universitaire Ziekenhuizen KU Leuven at 1 site in Belgium.
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 6 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 May 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Belgium. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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?
clinical patency of the hemodialysis extracorporeal circuit (time frame: 4 hours). 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 NCT04381234, 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 May 2020.