Acute Kidney InjuryPhase 4FFAKINCT02458157
Forced Fluid Removal in High Risk Acute Kidney Injury
A Phase 4 study testing Furosemide (Furix), Continuous renal replacement therapy (CRRT) and Resuscitation in people with Acute Kidney Injury and Fluid Overload, run by Nordsjaellands Hospital at 3 sites in Denmark.
Trial summary
The objective of this pilot trial is to assess the feasibility of forced fluid removal in patients admitted to the intensive care unit (ICU) with high-risk AKI and severe fluid overload. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Kidney Injury, Fluid Overload, Critical Illness
- What is being tested?
- Furosemide (Furix), Continuous renal replacement therapy (CRRT) and Resuscitation
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 21 participants
- Where
- 3 sitesDenmark
- Study dates
- Oct 2015to 8 Jun 2017
- Phase
- Phase 4
- 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
- Age ≥ 18 years of age
- Acute Kidney Injury defined according to the KDIGO criteria
- Renal Recovery Score ≤ 60%. (Calculated using www.renal-recovery-score.com)
- Fluid overload defined as a positive fluid balance ≥ 10% of ideal body weight.
- Able to undergo randomization within 12 hours of fulfilling other inclusion criteria
Who cannot join
- Known pre-hospitalization advanced chronic kidney disease. (eGFR < 30 mL/minute/1.73 m2 or chronic RRT.)
- Severe hypoxic respiratory failure (use of invasive ventilation and FiO2 > 80% and PEEP > 10 cm H2O)
- Severe burn injury (≥ 10% TBSA)
- Severe hypo- or hyper- natremia (< 120 or > 155 mmol/l)
- Hepatic coma
- Mentally disabled undergoing forced treatment
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- Pregnancy/breast feeding
- Lack of commitment for on-going life support including RRT
- Lack of informed consent
Trial locations and contacts
3 sites in 1 country.
Denmark3 sites
Aalborg Universitetshospital, Anæstesi og intensiv afdeling
Aalborg, 9000
Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.
Hillerød, 3400
Rigshospitale. ITA 4131 / Dept. of intensive care
København Ø, 2100
About this study
Official title: Forced Fluid Removal vs. Usual Intensive Care in High-risk Acute Kidney Injury With Severe Fluid Overload - A Randomized Controlled Trial
The objective of this pilot trial is to assess the feasibility of forced fluid removal in patients admitted to the intensive care unit (ICU) with high-risk AKI and severe fluid overload. The intervention will use furosemide infusion and/or continuous renal replacement therapy (CRRT) to achieve and maintain a neutral cumulative fluid balance. The intervention will be compared to standard of care as reflected in the kidney disease improving global outcome (KDIGO) guidelines.
Read the detailed description
Acute kidney injury (AKI) is a common and serious complication in patients admitted to ICU. A core element of critical care is resuscitation with crystalloid solutions. In many cases fluid accumulates and patients become fluid overloaded (positive fluid balance > 10% of bodyweight). This is especially true in patients with AKI, since they often have impaired ability to excrete salt and water. Most observational suggests harm with increased positive fluid balance.
Objectives: To assess feasibility of forced fluid removal with diuretics and/or CRRT in ICU patients with AKI and severe fluid overload, compared to current clinical practice.
Design: Multicentre, parallel group, randomized, assessor blinded pilot-trial with adequate generation of allocation sequence, and allocation concealment.
Trial Size: The pilot study is planned to include 50 patients. Inclusion is expected to start in August 2015.
- Conditions
- Acute Kidney Injury, Fluid Overload, Critical Illness
- Being tested
- Furosemide (Furix), Continuous renal replacement therapy (CRRT), Resuscitation, Usual Care
- Keywords
- ICU, Intensive, CRRT, Fluid Removal, AKI, Critical Care
- Medical subject headings
- Acute Kidney Injury, Edema, Critical Illness
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Furosemide (Furix)Drug
Also called Furix
- Loading dose: 40 mg I.V.
- Infusion rate 40 mg/h
- Continued until neutral cumulative fluid balance is achieved (the overall treatment goal) or average negative fluid balance is below 1 ml/kg/h for 8 hours.
Continuous renal replacement therapy (CRRT)Other
Also called CRRT
- Initiated in case of contraindications or inadequate effect of furosemide.
- Fluid removal is started at 2 ml/kg/h
- The efficacy is evaluated 3 times daily and removal rate increased by 0.5 ml/kg/h if the therapeutic goal is not achieved
ResuscitationOther
The physiologic response to fluid removal is monitored with three variables indicating inadequate circulation. These are:
- Mottling beyond the edge of kneecaps
- Hypotension (MAP < 50) resistant to inotropes and vasopressors
- Plasma lactate ≥ 4 mmol/l
Mottling and MAP are monitored continuously and lactate is measured routinely 4-6 times each day and on clinical indication. If one or more variable is present:
- Fluid removal is paused
- A crystalloid fluid bolus of 250-500 ml is given
- Circulatory status is reevaluated within 30 minutes
- Step 1-3 is repeated until signs of inadequate circulation have been resolved for minimum 1 hour
- Fluid removal is restarted in 25% reduced dose for minimum 4 hours before evaluation of effect.
Usual CareOther
All interventions are performed at the discretion of the treating physician apart from initiation of renal replacement therapy which is discouraged unless one or more of the following criteria are met:
- Hyperkalaemia (p-K+ > 6 mmol/l)
- Severe metabolic acidosis attributable to AKI (pH < 7.25 and standard base excess < -10 mmol/l) resistant to IV bicarbonate infusion
- Severe respiratory failure with PaO2/FiO2 < 13 kPa and bilateral infiltrates/oedema on the chest x-ray.
- Progressive azotaemia and a blood urea nitrogen (BUN) > 25 mmol/l.
| Study group | Role | What they receive |
|---|---|---|
| Forced Fluid Removal | Experimental | The experimental intervention is guided by a therapeutic goal of average negative fluid balance ≥ 1 ml/kg/h and safety variables indicating inadequate circulation (lactate ≥ 4, MAP < 50 or mottling beyond the edge of kneecaps).
The effect of fluid removal is evaluated three times daily (06:00. 14:00 and 22:00), while the safety variables are evaluated continuously. Resuscitation is started if one or more signs of inadequate circulation is present.
The first choice for fluid removal is diuretic therapy with furosemide, which is continued for a minimum of 8 hours. If the therapeutic goal (negative fluid balance ≥ 1 ml/kg/h) is not achieved and/or maintained by furosemide alone, then fluid removal with continuous renal replacement therapy (CRRT) is initiated. Receives: Drug: Furosemide (Furix); Other: Continuous renal replacement therapy (CRRT); Other: Resuscitation |
| Usual Care | Active comparator | Usual Care at the discretion of the treating clinicians, except for the initiation of renal replacement therapy (RRT). Receives: Other: Usual Care |
What is being measured
The primary outcome is the main question the study is designed to answer.
Cumulative fluid balance
Calculated as the sum of daily intake - daily output, as registered on the daily ICU observation charts.
Measured: 5 days
Secondary outcomes (5)
Cumulative fluid balance
participants will be followed for the duration of ICU stay, an expected average of 10 days
Measured: ICU stay expected average of 10 days
Mean daily fluid balance
participants will be followed for the duration of ICU stay, an expected average of 10 days
Measured: ICU stay expected average of 10 days
Major protocol violations
participants will be followed for the duration of ICU stay, an expected average of 10 days
Measured: ICU stay expected average of 10 days
Time to neutral cumulative fluid balance
No. of days until neutral cumulative fluid balance is achieved. Participants will be followed until neutral fluid balance is achieved or they reach the end of the observation period (90 days)
Measured: 90 days
Accumulated serious adverse reactions
Serious adverse reactions related to fluid removal(atrial fibrillation, ischemic events and organ failure), furosemide (severe electrolyte disturbance, severe thrombocytopenia, hearing loss agranulocytosis and allergic reactions) and the infusion of noradrenaline (cerebral hemorrhage, cardiac arrhythmia, psychiatric symptoms) will be examined
Measured: 90 days
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted1 Jun 2015 (estimated)
- Study startOct 2015
- Primary completion8 Jun 2017
- Study completion8 Jun 2017
Why it stopped: Very low recruitment rates
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (2)Papers the sponsor has linked to this study.
- Other trials for Acute Kidney InjuryStudies of the same condition, open and under way.
- 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 4
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Outcomes assessor
- Enrolment
- 21 participants (actual)
Sponsor and investigators
- Lead sponsor
- Nordsjaellands Hospital
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor
- Investigators
- Morten H Bestle, MD, Ph D, Principal investigator, Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.Anders Perner, Md, Ph D, Study chair, Rigshospitalet. ITA 4131 / Dept of Intensive CareJens-Ulrik Jensen, MD, Ph D, Study chair, Rigshospitalet, University of Copenhagen CHIP, Department of Infectious Diseases and Rheumatology, Section 2100Michael Ibsen, MD, Ph D, Study chair, Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.Rasmus E Berthelsen, MD, Study chair, Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02458157
- Sponsor's protocol ID
- FFAKI
- Other IDs
- 2015-001701-13, 2015
- Acronym
- FFAKI
- Status last verified
- Jul 2017
- First submitted
- 21 May 2015
- Last updated
- 6 Jul 2017
- Results posted
- No
- Data monitoring committee
- Yes
- Individual data sharing
- Undecided
Publications
Berthelsen RE, Perner A, Jensen AK, Rasmussen BS, Jensen JU, Wiis J, Behzadi MT, Bestle MH. Forced fluid removal in intensive care patients with acute kidney injury: The randomised FFAKI feasibility trial. Acta Anaesthesiol Scand. 2018 Aug;62(7):936-944. doi: 10.1111/aas.13124. Epub 2018 Apr 17.
PubMed 29664109Berthelsen RE, Itenov T, Perner A, Jensen JU, Ibsen M, Jensen AEK, Bestle M. Forced fluid removal versus usual care in intensive care patients with high-risk acute kidney injury and severe fluid overload (FFAKI): study protocol for a randomised controlled pilot trial. Trials. 2017 Apr 24;18(1):189. doi: 10.1186/s13063-017-1935-2.
PubMed 28438182
Study at a glance
From the registry record, last updated by the sponsor on 6 Jul 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Forced Fluid Removal vs. Usual Intensive Care in High-risk Acute Kidney Injury With Severe Fluid Overload - A Randomized Controlled Trial
- ClinicalTrials.gov ID
- NCT02458157
- Acronym / sponsor ID
- FFAKI / FFAKI
- Conditions
- Acute Kidney Injury, Fluid Overload, Critical Illness
- Keywords
- ICU, Intensive, CRRT, Fluid Removal, AKI, Critical Care
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Very low recruitment rates
- Enrolment
- 21 participants (actual)
- Lead sponsor
- Nordsjaellands HospitalUniversity, hospital or other
- Collaborators
- Copenhagen University Hospital, Rigshospitalet, Aalborg University Hospital
- Study start
- Oct 2015
- Primary completion
- 8 Jun 2017 (actual)
- Study completion
- 8 Jun 2017 (actual)
- First posted
- 1 Jun 2015 (estimated)
- 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 objective of this pilot trial is to assess the feasibility of forced fluid removal in patients admitted to the intensive care unit (ICU) with high-risk AKI and severe fluid overload. The intervention will use furosemide infusion and/or continuous renal replacement therapy (CRRT) to achieve and maintain a neutral cumulative fluid balance. The intervention will be compared to standard of care as reflected in the kidney disease improving global outcome (KDIGO) guidelines.
Detailed description
Acute kidney injury (AKI) is a common and serious complication in patients admitted to ICU. A core element of critical care is resuscitation with crystalloid solutions. In many cases fluid accumulates and patients become fluid overloaded (positive fluid balance > 10% of bodyweight). This is especially true in patients with AKI, since they often have impaired ability to excrete salt and water. Most observational suggests harm with increased positive fluid balance.
Objectives: To assess feasibility of forced fluid removal with diuretics and/or CRRT in ICU patients with AKI and severe fluid overload, compared to current clinical practice.
Design: Multicentre, parallel group, randomized, assessor blinded pilot-trial with adequate generation of allocation sequence, and allocation concealment.
Trial Size: The pilot study is planned to include 50 patients. Inclusion is expected to start in August 2015.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Forced Fluid Removal | Experimental | Drug: Furosemide (Furix), Other: Continuous renal replacement therapy (CRRT), Other: ResuscitationThe experimental intervention is guided by a therapeutic goal of average negative fluid balance ≥ 1 ml/kg/h and safety variables indicating inadequate circulation (lactate ≥ 4, MAP < 50 or mottling beyond the edge of kneecaps). The effect of fluid removal is evaluated three times daily (06:00. 14:00 and 22:00), while the safety variables are evaluated continuously. Resuscitation is started if one or more signs of inadequate circulation is present. The first choice for fluid removal is diuretic therapy with furosemide, which is continued for a minimum of 8 hours. If the therapeutic goal (negative fluid balance ≥ 1 ml/kg/h) is not achieved and/or maintained by furosemide alone, then fluid removal with continuous renal replacement therapy (CRRT) is initiated. |
| Usual Care | Active comparator | Other: Usual CareUsual Care at the discretion of the treating clinicians, except for the initiation of renal replacement therapy (RRT). |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Age ≥ 18 years of age
- Acute Kidney Injury defined according to the KDIGO criteria
- Renal Recovery Score ≤ 60%. (Calculated using www.renal-recovery-score.com)
- Fluid overload defined as a positive fluid balance ≥ 10% of ideal body weight.
- Able to undergo randomization within 12 hours of fulfilling other inclusion criteria
Key exclusion criteria (9 listed)
- Known pre-hospitalization advanced chronic kidney disease. (eGFR < 30 mL/minute/1.73 m2 or chronic RRT.)
- Severe hypoxic respiratory failure (use of invasive ventilation and FiO2 > 80% and PEEP > 10 cm H2O)
- Severe burn injury (≥ 10% TBSA)
- Severe hypo- or hyper- natremia (< 120 or > 155 mmol/l)
- Hepatic coma
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 |
|---|---|---|
| Furosemide (Furix)Also: Furix* Loading dose: 40 mg I.V. * Infusion rate 40 mg/h * Continued until neutral cumulative fluid balance is achieved (the overall treatment goal) or average negative fluid balance is below 1 ml/kg/h for 8 hours. | Drug | Forced Fluid Removal |
| Continuous renal replacement therapy (CRRT)Also: CRRT* Initiated in case of contraindications or inadequate effect of furosemide. * Fluid removal is started at 2 ml/kg/h * The efficacy is evaluated 3 times daily and removal rate increased by 0.5 ml/kg/h if the therapeutic goal is not achieved | Other | Forced Fluid Removal |
| ResuscitationThe physiologic response to fluid removal is monitored with three variables indicating inadequate circulation. These are: * Mottling beyond the edge of kneecaps * Hypotension (MAP < 50) resistant to inotropes and vasopressors * Plasma lactate ≥ 4 mmol/l Mottling and MAP are monitored continuously and lactate is measured routinely 4-6 times each day and on clinical indication. If one or more variable is present: 1. Fluid removal is paused 2. A crystalloid fluid bolus of 250-500 ml is given 3. Circulatory status is reevaluated within 30 minutes 4. Step 1-3 is repeated until signs of inadequate circulation have been resolved for minimum 1 hour 5. Fluid removal is restarted in 25% reduced dose for minimum 4 hours before evaluation of effect. | Other | Forced Fluid Removal |
| Usual CareAll interventions are performed at the discretion of the treating physician apart from initiation of renal replacement therapy which is discouraged unless one or more of the following criteria are met: * Hyperkalaemia (p-K+ > 6 mmol/l) * Severe metabolic acidosis attributable to AKI (pH < 7.25 and standard base excess < -10 mmol/l) resistant to IV bicarbonate infusion * Severe respiratory failure with PaO2/FiO2 < 13 kPa and bilateral infiltrates/oedema on the chest x-ray. * Progressive azotaemia and a blood urea nitrogen (BUN) > 25 mmol/l. | Other | Usual Care |
Primary outcome
Cumulative fluid balance
Time frame: 5 days
Calculated as the sum of daily intake - daily output, as registered on the daily ICU observation charts.
5 secondary outcomes
Cumulative fluid balance
Time frame: ICU stay expected average of 10 days
Mean daily fluid balance
Time frame: ICU stay expected average of 10 days
Major protocol violations
Time frame: ICU stay expected average of 10 days
Time to neutral cumulative fluid balance
Time frame: 90 days
Accumulated serious adverse reactions
Time frame: 90 days
Results and safety
The study was stopped early (reason given: Very low recruitment rates). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 6 Jul 2017.
- Derived from this study: PubMed 29664109Berthelsen RE, Perner A, Jensen AK, Rasmussen BS, Jensen JU, Wiis J, Behzadi MT, Bestle MH. Forced fluid removal in intensive care patients with acute kidney injury: The randomised FFAKI feasibility trial. Acta Anaesthesiol Scand. 2018 Aug;62(7):936-944. doi: 10.1111/aas.13124. Epub 2018 Apr 17.
- Derived from this study: PubMed 28438182Berthelsen RE, Itenov T, Perner A, Jensen JU, Ibsen M, Jensen AEK, Bestle M. Forced fluid removal versus usual care in intensive care patients with high-risk acute kidney injury and severe fluid overload (FFAKI): study protocol for a randomised controlled pilot trial. Trials. 2017 Apr 24;18(1):189. doi: 10.1186/s13063-017-1935-2.
- Individual participant dataSharing planned: Undecided
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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.
Morten H Bestle, MD, Ph D principal investigator
Nordsjællands Hospital. Dept. of Anaesthesiology and Intensive Care.
Anders Perner, Md, Ph D study chair
Rigshospitalet. ITA 4131 / Dept of Intensive Care
Jens-Ulrik Jensen, MD, Ph D study chair
Rigshospitalet, University of Copenhagen CHIP, Department of Infectious Diseases and Rheumatology, Section 2100
3 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 4 study testing Furosemide (Furix), Continuous renal replacement therapy (CRRT) and Resuscitation in people with Acute Kidney Injury and Fluid Overload, run by Nordsjaellands Hospital at 3 sites in Denmark.
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 5 inclusion and 9 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: stopped early, as of the sponsor's last update on 6 Jul 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 3 sites in Denmark. 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 4 studies take place after a treatment is approved, to learn more about its long-term benefits and risks in everyday use.
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 was stopped early (reason given: Very low recruitment rates). Results are not available in the source record.
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?
Cumulative fluid balance (time frame: 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 NCT02458157, which also lists 2 linked publications.
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 6 Jul 2017.