Effect of Add-on Spironolactone to Losartan Versus Losartan Alone on Peritoneal Membrane Among Peritoneal Dialysis Patients

NCT03953950 | Unknown Phase 4 DMC

• 1 other identifier: THOR Study Group
• Study Type: interventional
• Target: 84
• Locations: 1 country
• Sites: 1

Brief Summary

The ESCAPE-PD (Effects of add-on SpironolaCtone to losartan versus Alone on Peritoneal mEmbrane among continuous ambulatory Peritoneal Dialysis patients) study is a randomized, open-label, single center, active-controlled clinical trial. Adults end-stage kidney disease patients 18 years or older undergoing continuous ambulatory peritoneal dialysis (CAPD) will be enrolled. A total 84 CAPD will be randomly assigned to either the combination of spironolactone and losartan (experimental arm) or losartan alone (control arm). The primary outcomes are the difference in peritoneal dialysate effluent cancer antigen-125 (CA-125) and peritoneal equilibration test (PET) indices (dialysate-to-plasma creatinine ratio, 4-hour ultrafiltration volume, and the concentration of glucose present in the solution at the start of the test). Secondary outcome measures include laboratory and mechanistic outcome measures, nutrition outcomes, health-related quality of life, physical function, clinical events, and safety profiles. Results will be disseminated to suggest a strategy to prevent the peritoneal membrane function among CAPD patients through peer-reviewed publications along with scientific meetings.

Conditions

End Stage Renal Disease; Peritoneal Dialysis

Keywords

Peritoneal Dialysis; Peritoneal Membrane; Spironolactone; Losartan; Renin-Angiotensin-Aldosterone System

Outcome Measures

Primary Outcomes (2)

• Peritoneal dialysate effluent CA-125

  Using a commercial microparticle enzyme-linked immunosorbent assay

  6 months

• PET indices

  PET indices including dialysate-to-plasma creatinine ratio \[D/P Cr\], 4-hour ultrafiltration (UF) volume, and the concentration of glucose present in the solution at the start of the test \[D/D0\]) measured using a modified PET method (performed using 2,000 mL of 2.5% glucose solution).

  6 months

Secondary Outcomes (13)

• Changes in dialysate adequacy by Weekly kt/V

  6 months

• Changes in dialysate adequacy by weekly creatinine clearance

  6 months

• Changes in serum albumin concentration

  6 months

• Changes in serum potassium concentration

  6 months

• Changes in waist circumference

  6 months

Other Outcomes (4)

• Changes in blood pressure

  6 months

• Incidence of PD technique failure

  6 months

• Incidence of PD-related infections

  6 months

Study Arms (2)

Combination of spironolactone and losartan

EXPERIMENTAL

Drug: Spironolactone; Drug: Losartan

Losartan Alone

ACTIVE COMPARATOR

Drug: Losartan

Interventions

Spironolactone DRUG

Spironolactone Starting dose: 25 mg/day Target dose: 100 mg/day Titration: every 1-2 weeks, based on BP (keep\< 140/90 mmHg, but avoid hypotension \<90/60 mmHg), and serum potassium level (\<5.5 milliequivalent /liter)

Combination of spironolactone and losartan

Losartan DRUG

Losartan Starting dose: 50 mg/day Target dose: 100 mg/day Titration: every 1-2 weeks, based on BP (keep\< 140/90 mmHg, but avoid hypotension \<90/60 mmHg), and serum potassium level (\<5.5 milliequivalent /liter)

Combination of spironolactone and losartan; Losartan Alone

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• Age ≥ 18 years or older (both male and female patients)
• Incidence or prevalent end-stage kidney disease patients undergoing CAPD
• Had standard dialysis prescription for at least 30 days before screening
• History of hypertension
• Stable clinical condition without any inflammation at least 4 weeks prior to enrolment
• Had an ability to understand and willingness to sign an informed consent statement

You may not qualify if:

• Serum potassium concentration of ≥ 5.5 milliequivalent /liter
• History of severe or active cardiovascular and/or cerebrovascular disease
• History of renal artery stenosis
• Uncontrolled hypertension
• Contraindication to angiotensin-converting enzyme inhibitors/angiotensin II receptor blockers or mineralocorticoid receptor antagonists
• Pregnancy
• Recent PD-related peritonitis or exit-site and tunnel infection (within 2 months of screening)
• Had planned to have kidney transplantation or transfer to other PD centers with 6 months
• Prognosis for survival less than 12 months
• Any conditions (both mental or physical) that would interfere with the participant's ability to comply with the study protocol
• Any disease of the abdominal wall, such as injury or surgery, burns, hernia, dermatitis, inflammatory bowel diseases (Crohn's disease, ulcerative colitis or diverticulitis) that in the opinion of the Investigator would preclude the patient from being able to have PD
• Any intra-abdominal tumors or intestinal obstruction
• Current or recent (within 30 days) exposure to others investigational medicinal products

Sponsors & Collaborators

• Chiang Mai University: lead

Study Sites (1)

Pharmacoepidemiology and Statistics Research Center, Faculty of Pharmacy, Chiang Mai University

Chiang Mai, 50200, Thailand

Location

Related Publications (1)

• Hasegawa T, Nishiwaki H, Ota E, Levack WM, Noma H. Aldosterone antagonists for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev. 2021 Feb 15;2(2):CD013109. doi: 10.1002/14651858.CD013109.pub2.

  PMID: 33586138 DERIVED

MeSH Terms

Conditions

Kidney Failure, Chronic

Interventions

Spironolactone; Losartan

Condition Hierarchy (Ancestors)

Renal Insufficiency, Chronic; Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Chronic Disease; Disease Attributes; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Lactones; Organic Chemicals; Pregnenes; Pregnanes; Steroids; Fused-Ring Compounds; Polycyclic Compounds; Biphenyl Compounds; Benzene Derivatives; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Imidazoles; Azoles; Heterocyclic Compounds, 1-Ring; Heterocyclic Compounds; Tetrazoles

Study Design

• Study Type: interventional
• Phase: phase 4
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Study Record Dates

• First Submitted: April 20, 2019
• First Posted: May 17, 2019
• Study Start: October 1, 2019
• Primary Completion: September 1, 2020
• Study Completion: December 1, 2020
• Last Updated: September 4, 2019

Record last verified: 2019-08

Locations

TH (1)