AKINCT04762524
The Impact of CRRT Modality on Filter Life
A study testing CVVH vs CVVHD in people with AKI, run by University of Iowa at 1 site in United States.
Trial summary
The investigators plan to start patients who need CRRT on either CVVH or CVVHD by block randomization, and then to measure filter life. Read more about this study
- Who is it for?
- Ages 18 to 89 years
- Conditions the study is for
- AKI
- What is being tested?
- CVVH vs CVVHD
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 192 participants
- Where
- 1 siteUnited States
- Study dates
- 21 Mar 2020to 11 Mar 2021
- Phase
- Interventional
- 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 to 89 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Adult patients initiated on CRRT at University of Iowa Hospital
Who cannot join
- Prisoners
- Minors
- ECMO use at the time of CRRT initiation
Trial locations and contacts
1 site in 1 country.
About this study
The investigators plan to start patients who need CRRT on either CVVH or CVVHD by block randomization, and then to measure filter life.
Read the detailed description
Continuous renal replacement therapy (CRRT) is a dialysis modality used in critically ill intensive care unit (ICU) patients because it is associated with less hemodynamic instability than traditional hemodialysis. CRRT can be conducted using one of two different modalities, which are continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD). CVVH used conductive clearance, whereas CVVHD uses diffusive clearance (CVVHD).
In CVVH, plasma water is removed across the filter using transmembrane pressure which forces fluid into the effluent space. Solutes are removed via "solvent drag", which is the process by which solutes follow fluid flow. The rate of fluid removal is high (usually around 2-3 L/hr), and so hemodynamic collapse would quickly occur in the fluid were not replaced. The patient is therefore given "replacement fluid" which can be given pre-filter or post-filter, and usually nearly matches the fluid removal rate. For instance, if 2 L are removed per hour, 2 L are given back in the form of replacement fluid, if volume neutrality is desired. If fluid removal is desired, 1.9 L (e.g) may be given back, resulting in the net loss of 0.1 L of fluid per hour. The composition of the replacement fluid determines the serum concentration. As an example, if 2 L of fluid with a potassium concentration of 6.0 mmol/L (a high amount, 4.0 is normal) is removed and replaced with 2 L of replacement fluid with a potassium concentration of 2 mmol/L, then 8 mmol of potassium will be "removed" per hour, and the potassium concentration of the serum will fall.
In CVVHD, dialysate flows in the effluent space, creating a gradient which leads to movement of solutes either into or out of the blood, depending on the gradient direction. For instance, if serum has a potassium concentration of 6 mmol/L, and the dialysate has a concentration of 2 mmol/L, potassium will move from the blood into the dialysate, until the dialysate concentration is also equal to 6 mmol/L. At that point, net potassium movement will be 0, as the concentration will be equal. As with CVVH, with a dialysate flow rate of 2 L/hr will result in the removal of 8 mmol of potassium per hour. While these technical details concern only the specialist, the important take away is that both of these modalities achieve equivalent clearance, via different mechanisms. Notably, there are no differences in clinical outcomes with use of one or the other modality, and these modalities are currently thought to have complete equipoise. The decision is generally based on provider comfort and preference. There is no clinical scenario where one modality would be preferable to the other, based on current evidence.
A major issue when using CRRT is filter clotting, which occurs on average every 30 hours. Clotting renders the circuit unusable, and requires that the machine be reset, which is a process that takes 1-2 hours on average, and potentially longer depending on the availability of the dialysis nurses who change the circuits. This results in less delivery of dialysis than what is prescribed, and clotting is often also associated with the loss of the blood that is clotted in the circuit. This could be up to 150 ccs, which is a potentially significant amount in critically ill patients. As noted within the figures, post-filter CVVH is associated with hemoconcentration, and is thought to be associated with more clotting than CVVHD, where no hemoconcentration occurs. The situation is more complicated in pre-filter CVVH, however. As in Figure 3, the fluid is initially diluted, and then the fluid is removed over the course of flow through the filter. Some Nephrologists believe that this initial dilution of the blood results in decreased risk of clotting. However, other nephrologists believe that due to differential flow rates in the blood and replacement fluid that hemoconcentration still occurs within the filter, albeit to a much lesser degree than in post-filter CVVH (this argument is difficult to explain conceptually to a lay audience, but an attempt is made within Figure 3). It is therefore unclear currently whether pre-filter CVVH and CVVHD have equal or unequal rates of clotting. Because centers tend to use exclusively one modality or the other (or a combination, which is beyond the scope of this summary), retrospective analyses are often not possible due to lack of a comparison group.
Figure 3. In pre-filter CVVH, replacement fluid is administered prior to the blood passing through the filter. Nephrologists argue about the effect this has on the rates of hemoconcentration. Some would argue that after the initial dilution, the blood only returns to its initial concentration by the end of the filter, and thus over the course of the filter, there is actually hemodilution that decreases likelihood of clotting. Other nephrologists argue like so: With a blood flow rate of 12 L/hr (standard), and a fluid flow rate of 2 L/hr, then 14 L/hr enter the fluid, and 2 L/hr are removed, which is 14% (2/14) of the fluid that entered. If the fluid flow rate is increased to 4 L/hr, then 16 L /hr enter the filter, and 4L/hr are removed, which is 25% (4/16). This would therefore theoretically result in higher degrees of clotting. The question of pre-filter CVVH and its impact on clotting relative to CVVHD is therefore unanswered, and is the reason for the proposed study."
In short, the investigators plan to start patients who need CRRT on either CVVH or CVVHD by block randomization, and then to measure how often the filters on the machine need to be replaced.
The investigators plan to exclude minors, prisoners, and patients undergoing a certain procedure called "extracorporeal membrane oxygenation" (ECMO). ECMO is designed to pump blood and provide oxygen to the patient when the heart and lungs are not working correctly (ECMO attempts to do the work of the heart and lungs in instances where the patient's organs have failed). CRRT can be added to an ECMO circuit if renal failure is also present, but this is a specialized instance with unique risk factors for clotting, and is not representative of the general CRRT population.
- Conditions
- AKI
- Being tested
- CVVH vs CVVHD
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
CVVH vs CVVHDOther
Patients are initiated on CRRT in either the CVVH or CVVHD modality
| Study group | Role | What they receive |
|---|---|---|
| Initiation on CVVH | Experimental | Patients in this arm were initiated on CVVH, rather than CVVHD Receives: Other: CVVH vs CVVHD |
| Initiation on CVVHD | Active comparator | Patients in this arm were initiated on CVVHD, rather than CVVHDH Receives: Other: CVVH vs CVVHD |
What is being measured
The primary outcome is the main question the study is designed to answer.
Filter Life
Number of hours on average until filter clots
Measured: Until CRRT discontinuation, on average 4-5 days
Secondary outcomes (1)
Mortality
in-hospital mortality
Measured: Through hospital discharge, on average 2-4 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted21 Feb 2021
- Study start21 Mar 2020
- Primary completion1 Mar 2021
- Study completion11 Mar 2021
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 AKIStudies of the same condition, open and under way.
- More trials run by University of IowaThe 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 N/A
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Enrolment
- 192 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Iowa
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Benjamin Griffin, University of Iowa
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04762524
- Sponsor's protocol ID
- 201909716
- Status last verified
- Mar 2021
- First submitted
- 1 Feb 2021
- Last updated
- 16 Mar 2021
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Publications
Mann L, Ten Eyck P, Wu C, Story M, Jenigiri S, Patel J, Honkanen I, O'Connor K, Tener J, Sambharia M, Fraer M, Nourredine L, Somers D, Nizar J, Antes L, Kuppachi S, Swee M, Kuo E, Huang CL, Jalal DI, Griffin BR. CVVHD results in longer filter life than pre-filter CVVH: Results of a quasi-randomized clinical trial. PLoS One. 2023 Jan 11;18(1):e0278550. doi: 10.1371/journal.pone.0278550. eCollection 2023.
PubMed 36630406
Study at a glance
From the registry record, last updated by the sponsor on 16 Mar 2021. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Impact of CRRT Modality on Filter Life
- ClinicalTrials.gov ID
- NCT04762524
- Acronym / sponsor ID
- 201909716
- Conditions
- AKI
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 192 participants (actual)
- Lead sponsor
- University of IowaUniversity, hospital or other
- Study start
- 21 Mar 2020 (actual)
- Primary completion
- 1 Mar 2021 (actual)
- Study completion
- 11 Mar 2021 (actual)
- First posted
- 21 Feb 2021 (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.
The investigators plan to start patients who need CRRT on either CVVH or CVVHD by block randomization, and then to measure filter life.
Detailed description
Continuous renal replacement therapy (CRRT) is a dialysis modality used in critically ill intensive care unit (ICU) patients because it is associated with less hemodynamic instability than traditional hemodialysis. CRRT can be conducted using one of two different modalities, which are continuous venovenous hemofiltration (CVVH) and continuous venovenous hemodialysis (CVVHD). CVVH used conductive clearance, whereas CVVHD uses diffusive clearance (CVVHD).
In CVVH, plasma water is removed across the filter using transmembrane pressure which forces fluid into the effluent space. Solutes are removed via "solvent drag", which is the process by which solutes follow fluid flow. The rate of fluid removal is high (usually around 2-3 L/hr), and so hemodynamic collapse would quickly occur in the fluid were not replaced. The patient is therefore given "replacement fluid" which can be given pre-filter or post-filter, and usually nearly matches the fluid removal rate. For instance, if 2 L are removed per hour, 2 L are given back in the form of replacement fluid, if volume neutrality is desired. If fluid removal is desired, 1.9 L (e.g) may be given back, resulting in the net loss of 0.1 L of fluid per hour. The composition of the replacement fluid determines the serum concentration. As an example, if 2 L of fluid with a potassium concentration of 6.0 mmol/L (a high amount, 4.0 is normal) is removed and replaced with 2 L of replacement fluid with a potassium concentration of 2 mmol/L, then 8 mmol of potassium will be "removed" per hour, and the potassium concentration of the serum will fall.
In CVVHD, dialysate flows in the effluent space, creating a gradient which leads to movement of solutes either into or out of the blood, depending on the gradient direction. For instance, if serum has a potassium concentration of 6 mmol/L, and the dialysate has a concentration of 2 mmol/L, potassium will move from the blood into the dialysate, until the dialysate concentration is also equal to 6 mmol/L. At that point, net potassium movement will be 0, as the concentration will be equal. As with CVVH, with a dialysate flow rate of 2 L/hr will result in the removal of 8 mmol of potassium per hour. While these technical details concern only the specialist, the important take away is that both of these modalities achieve equivalent clearance, via different mechanisms. Notably, there are no differences in clinical outcomes with use of one or the other modality, and these modalities are currently thought to have complete equipoise. The decision is generally based on provider comfort and preference. There is no clinical scenario where one modality would be preferable to the other, based on current evidence.
A major issue when using CRRT is filter clotting, which occurs on average every 30 hours. Clotting renders the circuit unusable, and requires that the machine be reset, which is a process that takes 1-2 hours on average, and potentially longer depending on the availability of the dialysis nurses who change the circuits. This results in less delivery of dialysis than what is prescribed, and clotting is often also associated with the loss of the blood that is clotted in the circuit. This could be up to 150 ccs, which is a potentially significant amount in critically ill patients. As noted within the figures, post-filter CVVH is associated with hemoconcentration, and is thought to be associated with more clotting than CVVHD, where no hemoconcentration occurs. The situation is more complicated in pre-filter CVVH, however. As in Figure 3, the fluid is initially diluted, and then the fluid is removed over the course of flow through the filter. Some Nephrologists believe that this initial dilution of the blood results in decreased risk of clotting. However, other nephrologists believe that due to differential flow rates in the blood and replacement fluid that hemoconcentration still occurs within the filter, albeit to a much lesser degree than in post-filter CVVH (this argument is difficult to explain conceptually to a lay audience, but an attempt is made within Figure 3). It is therefore unclear currently whether pre-filter CVVH and CVVHD have equal or unequal rates of clotting. Because centers tend to use exclusively one modality or the other (or a combination, which is beyond the scope of this summary), retrospective analyses are often not possible due to lack of a comparison group.
Figure 3. In pre-filter CVVH, replacement fluid is administered prior to the blood passing through the filter. Nephrologists argue about the effect this has on the rates of hemoconcentration. Some would argue that after the initial dilution, the blood only returns to its initial concentration by the end of the filter, and thus over the course of the filter, there is actually hemodilution that decreases likelihood of clotting. Other nephrologists argue like so: With a blood flow rate of 12 L/hr (standard), and a fluid flow rate of 2 L/hr, then 14 L/hr enter the fluid, and 2 L/hr are removed, which is 14% (2/14) of the fluid that entered. If the fluid flow rate is increased to 4 L/hr, then 16 L /hr enter the filter, and 4L/hr are removed, which is 25% (4/16). This would therefore theoretically result in higher degrees of clotting. The question of pre-filter CVVH and its impact on clotting relative to CVVHD is therefore unanswered, and is the reason for the proposed study."
In short, the investigators plan to start patients who need CRRT on either CVVH or CVVHD by block randomization, and then to measure how often the filters on the machine need to be replaced.
The investigators plan to exclude minors, prisoners, and patients undergoing a certain procedure called "extracorporeal membrane oxygenation" (ECMO). ECMO is designed to pump blood and provide oxygen to the patient when the heart and lungs are not working correctly (ECMO attempts to do the work of the heart and lungs in instances where the patient's organs have failed). CRRT can be added to an ECMO circuit if renal failure is also present, but this is a specialized instance with unique risk factors for clotting, and is not representative of the general CRRT population.
Study design
- Primary purpose
- Supportive care
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Initiation on CVVH | Experimental | Other: CVVH vs CVVHDPatients in this arm were initiated on CVVH, rather than CVVHD |
| Initiation on CVVHD | Active comparator | Other: CVVH vs CVVHDPatients in this arm were initiated on CVVHD, rather than CVVHDH |
Who may qualify
- Ages
- 18 to 89 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (1 listed)
- Adult patients initiated on CRRT at University of Iowa Hospital
Key exclusion criteria (3 listed)
- Prisoners
- Minors
- ECMO use at the time of CRRT initiation
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 |
|---|---|---|
| CVVH vs CVVHDPatients are initiated on CRRT in either the CVVH or CVVHD modality | Other | Initiation on CVVH, Initiation on CVVHD |
Primary outcome
Filter Life
Time frame: Until CRRT discontinuation, on average 4-5 days
Number of hours on average until filter clots
1 secondary outcome
Mortality
Time frame: Through hospital discharge, on average 2-4 weeks
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 16 Mar 2021.
- Derived from this study: PubMed 36630406Mann L, Ten Eyck P, Wu C, Story M, Jenigiri S, Patel J, Honkanen I, O'Connor K, Tener J, Sambharia M, Fraer M, Nourredine L, Somers D, Nizar J, Antes L, Kuppachi S, Swee M, Kuo E, Huang CL, Jalal DI, Griffin BR. CVVHD results in longer filter life than pre-filter CVVH: Results of a quasi-randomized clinical trial. PLoS One. 2023 Jan 11;18(1):e0278550. doi: 10.1371/journal.pone.0278550. eCollection 2023.
- 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.
The record lists no contact. Use the official record to reach the sponsor.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing CVVH vs CVVHD in people with AKI, run by University of Iowa at 1 site in United States.
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 1 inclusion and 3 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 16 Mar 2021. 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 United States. 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.
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?
Filter Life (time frame: Until CRRT discontinuation, on average 4-5 days). 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 NCT04762524, 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 16 Mar 2021.