The LIPMAT Study: Liposomal Prednisolone to Improve Hemodialysis Fistula Maturation (LIPMAT)

This study will investigate if liposomal prednisolone is effective in promoting arteriovenous fistula (AVF) maturation when administered to human subjects after surgical creation of a radio-cephalic AVF.

Study Overview

• Status: Terminated
• Conditions: Renal Dialysis; Hemodynamics; Neointima; Vascular Remodeling
• Intervention / Treatment: Drug: Placebo; Drug: PEG-liposomal prednisolone sodium phosphate

Detailed Description

AVFs are the preferred means of vascular access for maintenance hemodialysis. Nonmaturation occurs in 30-50% of cases, with highest rates in radio-cephalic fistulas. Inflammatory cytokines are involved in this process of nonmaturation. By suppressing inflammation, corticosteroids might promote maturation, but have significant systemic side effects. Liposomal prednisolone has a long circulation time and targets inflamed tissue with low systemic concentrations and limited side effects. In an animal study, it was demonstrated to promote AVF maturation. At present, no drug therapy aimed at improving shunt maturation is available. This study will investigate if liposomal prednisolone is effective in promoting AVF maturation when administered to human subjects after surgical creation of a radio-cephalic AVF.

• Study Type: Interventional
• Enrollment (Actual): 30
• Phase: Phase 2

Contacts and Locations

Study Locations

• Netherlands
  • Zuid Holland
    • Leiden, Zuid Holland, Netherlands, 2333 ZA
      • Leiden University Medical Center

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (ADULT, OLDER_ADULT)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

1. Patients who are scheduled for creation of a radiocephalic AVF for maintenance hemodialysis.
2. Male or female ≥ 18 years old.
3. Patients are able and willing to give written informed consent.

Exclusion Criteria:

1. Any concurrent illness, disability or clinically significant abnormality that may, as judged by the investigator, affect the interpretation of clinical efficacy or safety data or prevent the subject from safely completing the assessments required by the protocol.
2. Current participation in another interventional clinical trial or subjects who have received an investigational drug within 30 days prior to the baseline visit.
3. History of psychosis.
4. History of osteonecrosis
5. Previous AVF in the ipsilateral arm.
6. Current central venous catheter at the ipsilateral side.
7. Treatment with oral, rectal or injectable (including intra-articular) glucocorticoids (CS) within 6 weeks prior to baseline visit. Inhaled glucocorticoids are allowed. Topical steroids are allowed, however subjects should not have received more than 100 gram of a mild to moderate topical corticosteroid cream per week, 50 gram of a potent corticosteroid cream per week or 30 gram of a very potent topical corticosteroid cream per week in the 4 weeks prior to the baseline visit.
8. Treatment with immunosuppressant drugs. Treatment with non-steroidal anti-inflammatory drugs (NSAIDs).
9. Patients who are unlikely to adequately comply with the trial's procedures (due for instance to medical conditions likely to require an extended interruption or discontinuation, history of substance abuse or noncompliance).
10. Women who are lactating, pregnant (positive pregnancy test at baseline) or planning to become pregnant during the course of the study.
11. Unwillingness to use reliable and acceptable contraceptive methods throughout the study and till 3 months after last study medication except for female patients who are surgically sterile (bilateral tubal ligation, bilateral oophorectomy or hysterectomy) or at least 1 year postmenopausal.
12. Malignant disease, unless cured. Current prostate carcinoma without current or planned cytostatic therapy is allowed.
13. Uncontrolled Diabetes mellitus.
14. Signs of active infection, requiring systemic treatment.
15. Positive Quantiferon test.
16. Subject with positive hepatitis panel (including hepatitis B surface antigen [HBsAg], and / or anti-hepatitis B core antibodies, and / or hepatitis C virus antibody [anti-HCV]).
17. History of anaphylaxis or severe allergic responses, including to radio-contrast agents.
18. Planned live-virus vaccinations.
19. Planned surgical interventions or planned elective hospital admissions within 6 weeks after AVF surgery. Planned hemodialysis sessions do not count as an exclusion criterion.
20. Abnormal hepatic function (Alanine aminotransferase (ALT)/ aspartate aminotransferase (AST) or bilirubin > 2 x upper limit of normal) at the time of the screening visit.
21. Clinically significant out-of-range values on hematology panel, at discretion of the Principal Investigator.
22. Current substance abuse or alcohol abuse.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: TREATMENT
• Allocation: RANDOMIZED
• Interventional Model: PARALLEL
• Masking: QUADRUPLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Liposomal prednisolone; Treatment with polyethylene glycol (PEG)-liposomal prednisolone sodium phosphate 150mg in 500ml saline intravenously at 1 and 15 days post surgery.	Drug: PEG-liposomal prednisolone sodium phosphate; Liposomal prednisolone; Other Names: Nanocort
Placebo Comparator: Placebo; Treatment with 500ml normal 0.9% saline intravenously at 1 and 15 days post surgery.	Drug: Placebo; 0.9% normal saline

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cephalic vein diameter	Echographic measurement of the diameter of the cephalic vein, six weeks after surgical creation of the radiocephalic shunt.	6 weeks after surgical creation of the radiocephalic shunt.

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Cephalic vein diameter	Echographic measurement of the diameter of the cephalic vein, three months after surgical creation of the radiocephalic shunt.	3 months after surgical creation of the radiocephalic shunt.
Radial artery diameter	Echographic measurement of the diameter of the radial artery, six weeks after surgical creation of the radiocephalic shunt.	6 weeks after surgical creation of the radiocephalic shunt.
Radial artery diameter	Echographic measurement of the diameter of the radial artery, three months after surgical creation of the radiocephalic shunt.	3 months after surgical creation of the radiocephalic shunt.
Radial artery flow.	Echographic measurement of the flow of the radial artery, six weeks after surgical creation of the radiocephalic shunt.	6 weeks after surgical creation of the radiocephalic shunt.
Radial artery flow.	Echographic measurement of the flow of the radial artery, three months after surgical creation of the radiocephalic shunt.	3 months after surgical creation of the radiocephalic shunt.

Collaborators and Investigators

• Sponsor: Leiden University Medical Center
• Collaborators: Academisch Medisch Centrum - Universiteit van Amsterdam (AMC-UvA); Medical Center Haaglanden; Reinier de Graaf Groep; Spaarne Gasthuis; OLVG; Alrijne Hospital; HagaZiekenhuis; Tergooi Ziekenhuis
• Investigators: Principal Investigator: Joris I Rotmans, MD PhD, Leiden University Medical Center

Study record dates

Study Major Dates

• Study Start: November 1, 2015
• Primary Completion (Actual): May 30, 2018
• Study Completion (Actual): May 30, 2018

Study Registration Dates

• First Submitted: July 2, 2015
• First Submitted That Met QC Criteria: July 8, 2015
• First Posted (Estimate): July 13, 2015

Study Record Updates

• Last Update Posted (Actual): September 18, 2018
• Last Update Submitted That Met QC Criteria: September 17, 2018
• Last Verified: May 1, 2018

More Information

Terms related to this study

• Keywords: Arteriovenous fistula; Hemodialysis; Vascular access; Shunt; Maturation; Arteriovenous shunt; Liposomal prednisolone; PEG-liposomal prednisolone sodium phosphate; Radio-cephalic
• Additional Relevant MeSH Terms: Pathologic Processes; Pathological Conditions, Anatomical; Fistula; Neointima; Vascular Remodeling; Physiological Effects of Drugs; Autonomic Agents; Peripheral Nervous System Agents; Anti-Inflammatory Agents; Antineoplastic Agents; Antiemetics; Gastrointestinal Agents; Glucocorticoids; Hormones; Hormones, Hormone Substitutes, and Hormone Antagonists; Antineoplastic Agents, Hormonal; Neuroprotective Agents; Protective Agents; Prednisolone; Methylprednisolone Acetate; Methylprednisolone; Methylprednisolone Hemisuccinate; Prednisolone acetate; Prednisolone hemisuccinate; Prednisolone phosphate
• Other Study ID Numbers: LIPMAT

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No