Conservative Dialysis Approach for Acute Kidney Injury

(LIBERATE-D Trial)

Recruiting at 3 trial locations

Overseen By Kathleen Liu, MD, PhD, MAS

Age: 18+

Sex: Any

Trial Phase: Academic

Sponsor: University of California, San Francisco

Disqualifiers: Liver disease, Nephrectomy, Heart failure, others

No Placebo Group All trial participants will receive the active study treatment (no placebo)

Approved in 6 Jurisdictions This treatment is already approved in other countries

Compensation: Varies

Number of Visits: Unknown

Duration: Up to 28 days

220 Participants Needed

What You Need to Know Before You Apply

What is the purpose of this trial?

The goal of the LIBERATE-D clinical trial is to improve outcomes for patients recovering from dialysis-requiring acute kidney injury (AKI-D). The impact of a conservative dialysis strategy compared to standard clinical practice of thrice-weekly dialysis will be examined to help generate knowledge for how to guide delivery of dialysis to facilitate renal recovery.

Will I have to stop taking my current medications?

The trial information does not specify whether you need to stop taking your current medications. It's best to discuss this with the trial coordinators or your doctor.

Is conservative dialysis generally safe for humans?

Continuous ambulatory peritoneal dialysis (CAPD) has been used for many years and is considered a safe treatment for kidney failure, with a relatively low mortality rate and manageable complications like peritonitis (infection of the abdominal lining). Automated peritoneal dialysis (APD) has also shown no major safety concerns in studies, with no fluid overload or significant abdominal discomfort reported. ^{1 2 3 4 5}

How does the Conservative Dialysis Approach for Acute Kidney Injury differ from other treatments?

The Conservative Dialysis Approach for Acute Kidney Injury is unique because it combines peritoneal dialysis (PD) and hemodialysis (HD) to address the limitations of PD alone, especially after the loss of residual renal function. This combination allows for better control of the uremic state and more effective solute removal, providing a more comprehensive treatment compared to using PD or HD alone. ^{6 7 8 9 10}

What data supports the effectiveness of the treatment for Conservative Dialysis Approach for Acute Kidney Injury?

Research shows that automated peritoneal dialysis (APD) is at least as effective as continuous ambulatory peritoneal dialysis (CAPD) for patients with end-stage kidney disease, with similar survival rates and no major differences in overall mortality. APD has been found to improve certain clinical outcomes like ultrafiltration and urea clearance compared to CAPD. ^{1 11 12 13 14}

Who Is on the Research Team?

Kathleen Liu, MD, PhD, MAS

Principal Investigator

University of California, San Francisco

Chi-yuan Hsu, MD, MSc

Principal Investigator

University of California, San Francisco

Are You a Good Fit for This Trial?

This trial is for adults over 18 with acute kidney injury needing dialysis, who are stable without vasopressor support and have a history of good kidney function. It's not for pregnant individuals, prisoners, those unable to consent or lacking a decision-maker, patients with certain other health conditions or treatments, or if they've been on dialysis for more than 3 months.

Inclusion Criteria

I don't need drugs to maintain my blood pressure and I am scheduled for occasional dialysis.

Your kidney function, as measured by eGFR, is at least 15 mL/min/1.73 m2.

I am hospitalized with acute kidney injury requiring dialysis, as diagnosed by my kidney doctor.

Exclusion Criteria

Pregnant

I need a device or continuous medication to support my heart's pumping.

I need dialysis for reasons other than kidney failure, like liver disease.

Timeline for a Trial Participant

Screening

Participants are screened for eligibility to participate in the trial

2-4 weeks

Treatment

Participants are randomized to either a conservative dialysis strategy or conventional thrice-weekly dialysis

Up to 28 days

Thrice-weekly visits for dialysis in the conventional arm

Follow-up

Participants are monitored for renal recovery and other outcomes after treatment

Up to 90 days

Long-term follow-up

Participants are monitored for all-cause mortality and other long-term outcomes

Up to 12 months

What Are the Treatments Tested in This Trial?

Interventions

• Dialysis

Trial Overview The LIBERATE-D study is testing whether less frequent dialysis (a conservative strategy) can be as effective as the standard three times weekly sessions in helping patients recover from acute kidney injury that required initial dialysis treatment.

How Is the Trial Designed?

Group I: Conservative Experimental Treatment 1 Intervention

Conservative dialysis strategy--dialysis prescribed only when specific metabolic or clinical indications are met. These indications are: blood urea nitrogen \>112 mg/dL (40 mmol/L; blood potassium concentration \>6 mmol/L; blood potassium concentration \>5.5 mmol/L despite medical treatment; arterial blood gas pH \<7.15, or in the absence of an available blood gas, serum bicarbonate \<12 mmol/L, acute pulmonary edema due to fluid overload, responsible for hypoxemia requiring oxygen flow rate \>5 L/min or equivalent via face mask/tracheostomy mask to maintain SpO2 \>95% or requiring FiO2 \>50% in patients with tracheostomy already on invasive or non-invasive mechanical ventilation and despite diuretic therapy; clinician judgement

Group II: Conventional Active Control 1 Intervention

Thrice-weekly intermittent dialysis until pre-specified criteria for recovery are met

Dialysis is already approved in European Union, United States, Canada, Japan, China, Switzerland for the following indications:

Approved in European Union as Dialysis for:

• Acute kidney injury
• Chronic kidney disease
• End-stage renal disease

Approved in United States as Dialysis for:

• Acute kidney injury
• Chronic kidney disease
• End-stage renal disease

Approved in Canada as Dialysis for:

• Acute kidney injury
• Chronic kidney disease
• End-stage renal disease

Approved in Japan as Dialysis for:

• Acute kidney injury
• Chronic kidney disease
• End-stage renal disease

Approved in China as Dialysis for:

• Acute kidney injury
• Chronic kidney disease
• End-stage renal disease

Approved in Switzerland as Dialysis for:

• Acute kidney injury
• Chronic kidney disease
• End-stage renal disease

Who Is Running the Clinical Trial?

University of California, San Francisco

Lead Sponsor

Trials

2,636

Recruited

19,080,000+

Vanderbilt University Medical Center

Collaborator

Trials

922

Recruited

939,000+

National Institutes of Health (NIH)

Collaborator

Trials

2,896

Recruited

8,053,000+

National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)

Collaborator

Trials

2,513

Recruited

4,366,000+

Published Research Related to This Trial

In a study of 305 patients undergoing continuous ambulatory peritoneal dialysis (CAPD) and continuous cycling peritoneal dialysis (CCPD), the overall patient survival rates were high, with 87.9% surviving at one year, 76.6% at two years, and 67.0% at three years.

Peritonitis remains a significant complication, being the leading cause of hospitalizations and transfers, although the peritonitis rate has improved from 1.9 to 1.2 episodes per patient-year, indicating progress in managing this condition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Chronic peritoneal dialysis: seven-year experience in a large Hispanic program. Saade, M., Joglar, F.[2020]

In a study of 270 patients (90 on automated peritoneal dialysis (APD) and 180 on continuous ambulatory peritoneal dialysis (CAPD)), APD showed better patient survival for those with a Charlson's score of 6 or lower, while those with a score of 7 or higher had worse survival on APD compared to CAPD.

The study found that comorbid diseases significantly influenced the effectiveness of the dialysis method, indicating that APD may be more beneficial for younger patients with fewer health issues, while CAPD may be preferable for those with more complex health conditions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated peritoneal dialysis in Hong Kong: there are two distinct groups of patients. Kwan, BC., Chow, KM., Ma, TK., et al.[2013]

Automated peritoneal dialysis (APD) is increasingly used for end-stage kidney disease (ESKD) patients and has become the most common method of peritoneal dialysis in high-income countries due to advancements in technique and technology.

APD is considered at least as effective as continuous ambulatory peritoneal dialysis (CAPD) in terms of major biomedical outcomes, but its effects on patient-reported outcomes require further investigation.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Automated Peritoneal Dialysis: Patient Perspectives and Outcomes. Domenici, A., Giuliani, A.[2021]

In a study of 649 incident dialysis patients (87 on automated peritoneal dialysis (APD) and 562 on continuous ambulatory peritoneal dialysis (CAPD)), there was no significant difference in overall mortality between the two groups over a 5-year follow-up period.

The analysis also showed no difference in technique failure rates, indicating that APD does not provide a clear advantage over CAPD in terms of patient survival or the need to switch dialysis modalities.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Similar survival on automated peritoneal dialysis and continuous ambulatory peritoneal dialysis in a large prospective cohort. Michels, WM., Verduijn, M., Boeschoten, EW., et al.[2021]

Automated peritoneal dialysis (APD), specifically the continuous cyclic peritoneal dialysis (CCPD) method, showed better ultrafiltration and urea clearance compared to traditional continuous ambulatory peritoneal dialysis (CAPD) in a study involving 3 patients over one year.

The study reported no signs of fluid overload or abdominal discomfort, indicating that APD is a safe alternative for uremic patients with complications like peritonitis, hernia, or procedural burnout.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Clinical experience of automated peritoneal dialysis]. Chuang, FR., Huang, CC., Fang, JT., et al.[2016]

Over 25 years, technique survival rates for continuous ambulatory peritoneal dialysis (CAPD) improved, with 5-year and 10-year survival rates at 71.9% and 48.1%, respectively, particularly for patients starting treatment after 1992 due to a decrease in peritonitis episodes.

Patient survival rates also improved significantly from 1981-1992 to 1992-2005, with 5-year and 10-year survival rates at 69.8% and 51.8%, although older age, diabetes, and cardiovascular issues remained significant risk factors for mortality.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Improving outcome of CAPD: twenty-five years' experience in a single Korean center. Han, SH., Lee, SC., Ahn, SV., et al.[2020]

Continuous ambulatory peritoneal dialysis (CAPD) is an effective long-term treatment for patients with end-stage kidney failure, highlighting its importance as a maintenance therapy.

As more patients undergo CAPD, it is crucial to investigate the complications associated with long-term use, including issues related to high intraabdominal pressure and the body's response to the dialysis solutions.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Non-infectious complications during treatment with continuous peritoneal dialysis (CAPD)]. Betkowska-Prokop, A.[2006]

In a one-year study of 20 patients undergoing continuous ambulatory peritoneal dialysis (CAPD), the mortality rate was low at 10%, indicating a relatively safe treatment option.

The study found that 75% of patients achieved adequate dialysis, with a stable peritonitis rate of 1 episode per 16.4 patient-months, suggesting that CAPD can be an effective alternative to hemodialysis in selected cases.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

[Results of treatment with continuous ambulatory peritoneal dialysis. One year observation]. Stompór, T., Sułowicz, W., Bucki, J.[2006]

In a study of 75 patients over one year, using automated blood culture systems significantly improved the detection of organisms causing peritonitis in continuous ambulatory peritoneal dialysis (CAPD), identifying 87 cases compared to only 53 with conventional methods.

The majority of peritonitis cases were caused by Gram-negative organisms (62.3%), and the study found that early detection through improved culture methods can lead to better outcomes, with a recovery rate of 77% among patients.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Continuous ambulatory peritoneal dialysis peritonitis: Microbiology and outcomes. Pindi, G., Kawle, V., Sunkara, RR., et al.[2023]

A patient with polycystic kidney disease successfully underwent nocturnal intermittent peritoneal dialysis (NIPD) for ten years, demonstrating its effectiveness as a long-term dialysis option when other therapies were unsuitable.

Adjustments to the dialysis regimen, including increasing the dialysis solution dose and optimizing outflow times, led to significant improvements in dialysis efficiency and patient outcomes, highlighting the importance of tailoring NIPD to individual needs.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Long-term successful nocturnal intermittent peritoneal dialysis: a ten-year case study. Trivedi, HS., Twardowski, ZJ.[2004]

Peritoneal dialysis (PD) offers comparable survival rates to hemodialysis (HD) and may even have advantages, making it a viable option for long-term renal replacement therapy.

Starting PD early can help preserve vascular access for future treatments, and the paper discusses strategies to minimize complications associated with PD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Peritoneal dialysis as a valuable tool for blood purification. Stegmayr, B.[2017]

A comprehensive literature review was conducted to assess the compatibility and stability of various drugs used in peritoneal dialysis (PD), which is crucial for treating conditions like peritonitis in patients with end-stage renal failure.

The findings provide clinicians with essential information on which drugs are stable in different PD solutions and containers, ensuring effective and safe treatment for patients undergoing PD.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Intraperitoneal administration of drugs in peritoneal dialysis patients: a review of compatibility and guidance for clinical use. de Vin, F., Rutherford, P., Faict, D.[2022]

Peritoneal dialysis (PD) effectively maintains stable electrolyte and acid-base balance while preserving residual renal function (RRF), making it a beneficial initial treatment for patients with kidney issues.

As RRF declines, combining PD with hemodialysis (HD) can enhance solute removal and ultrafiltration, leading to a more effective overall dialysis strategy that could allow for 'real' daily dialysis.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Complementary dialysis for daily dialysis. Kawanishi, H.[2007]

Combining peritoneal dialysis (PD) with once-weekly hemodialysis (PD+HD) significantly improves dialysis adequacy, as shown by increased weekly Kt/Vef from 1.55 to 2.27 and creatinine clearance from 42.0 to 60.3 L/1.73 m2 in patients without residual renal function (RRF).

PD+HD also enhances nutritional status, evidenced by a significant increase in serum albumin levels from 3.3 to 3.6 g/dL, while maintaining protein losses similar to those in PD alone, making it a recommended regimen for optimal dialysis and nutrition.

NCBI (Pubmed)

pubmed.ncbi.nlm.nih.gov

Evaluation of dialysis dose during combination therapy with peritoneal dialysis and hemodialysis. Kawanishi, H., Moriishi, M., Tsuchiya, S.[2013]

Citations

1. United States pubmed.ncbi.nlm.nih.gov

Chronic peritoneal dialysis: seven-year experience in a large Hispanic program. [2020]

2. Australia pubmed.ncbi.nlm.nih.gov

Automated peritoneal dialysis in Hong Kong: there are two distinct groups of patients. [2013]

3. New Zealand pubmed.ncbi.nlm.nih.gov

Automated Peritoneal Dialysis: Patient Perspectives and Outcomes. [2021]

4. United States pubmed.ncbi.nlm.nih.gov

Similar survival on automated peritoneal dialysis and continuous ambulatory peritoneal dialysis in a large prospective cohort. [2021]

5. China (Republic : 1949- ) pubmed.ncbi.nlm.nih.gov

[Clinical experience of automated peritoneal dialysis]. [2016]

6. United States pubmed.ncbi.nlm.nih.gov

Improving outcome of CAPD: twenty-five years' experience in a single Korean center. [2020]

7. Poland pubmed.ncbi.nlm.nih.gov

[Non-infectious complications during treatment with continuous peritoneal dialysis (CAPD)]. [2006]

8. Poland pubmed.ncbi.nlm.nih.gov

[Results of treatment with continuous ambulatory peritoneal dialysis. One year observation]. [2006]

9. United States pubmed.ncbi.nlm.nih.gov

Continuous ambulatory peritoneal dialysis peritonitis: Microbiology and outcomes. [2023]

10. Canada pubmed.ncbi.nlm.nih.gov

Long-term successful nocturnal intermittent peritoneal dialysis: a ten-year case study. [2004]

11. Germany pubmed.ncbi.nlm.nih.gov

Peritoneal dialysis as a valuable tool for blood purification. [2017]

12. United States pubmed.ncbi.nlm.nih.gov

Intraperitoneal administration of drugs in peritoneal dialysis patients: a review of compatibility and guidance for clinical use. [2022]

13. Switzerland pubmed.ncbi.nlm.nih.gov

Complementary dialysis for daily dialysis. [2007]

14. Canada pubmed.ncbi.nlm.nih.gov

Evaluation of dialysis dose during combination therapy with peritoneal dialysis and hemodialysis. [2013]