AzTrials
AzTrials

End Stage Renal DiseasePhase 4LAST-DNCT01855334

L-Arginine and Spironolactone Trial in Dialysis-Dependent ESRD

A Phase 4 study testing Spironolactone and L-arginine in people with End Stage Renal Disease and Hemodialysis, run by Brigham and Women's Hospital at 3 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
Search all trials

Trial summary

Cardiovascular disease is the primary cause of death in patients with end stage renal disease (ESRD). New research suggests that the high risk of death may be partly due to high levels of fibrosis and a loss of small blood vessels in the heart of patients with dialysis-dependent ESRD. Read more about this study

Who is it for?
Ages 18 to 85 years
Conditions the study is for
End Stage Renal Disease, Hemodialysis
What is being tested?
Spironolactone and L-arginine
Type of treatment
Pill or oral medicine
Could I receive a placebo?
Yes, some participants may receive a placebo
How many people
0 participants
Where
3 sitesUnited States
Study dates
Sep 2013to Jul 2018
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 to 85 years
  • All sexes
  • No healthy volunteers
  • Adult, Older adult

Who may be able to join

  • Chronic dialysis therapy for End Stage Renal Disease
  • Age 21-85

Who cannot join

  • Hyperkalemia requiring unscheduled dialysis within 3 months
  • Pre-dialysis potassium ≥6.5 meq/L within 3 months
  • Hypotension defined as SBP <100
  • Recurrent intra-dialytic hypotension defined as recurrent cramping, light-headedness, or hypotension requiring infusion of saline or other intervention or otherwise limiting ability to achieve dry weight. Or SBP <80
  • History of myocardial infarction
  • History of coronary artery bypass surgery
Show all 17Show fewer
  • Non revascularized coronary disease >90%
  • Mitral valve repair or replacement
  • Severe mitral valve disease
  • Renal transplant expected within 9 months
  • Expected survival < 9 months
  • Pregnant
  • Prisoners
  • Unable to provide consent
  • Allergy to spironolactone or L-arginine
  • Digitalis use
  • 1st or 2nd degree heart block

Trial locations and contacts

3 sites in 1 country.

United States3 sites

  • Massachusetts General Hospital

    Boston, Massachusetts, 021114

  • Brigham & Women's Hospital

    Boston, Massachusetts, 02120

  • Beth Israel Deaconess Medical Center

    Boston, Massachusetts, 02215

Other trials in United States

About this study

Official title: A Randomized, Controlled Trial of L-arginine and Spironolactone in Dialysis-dependant End Stage Renal Disease

Cardiovascular disease is the primary cause of death in patients with end stage renal disease (ESRD). New research suggests that the high risk of death may be partly due to high levels of fibrosis and a loss of small blood vessels in the heart of patients with dialysis-dependent ESRD. This study is designed to compare the effects of two different drugs, spironolactone and L-arginine, with placebo on structure and function of the heart in individuals with dialysis-dependent ESRD.

Read the detailed description

We hypothesize that that abnormalities in aldosterone and nitric oxide (NO) homeostasis contribute to the progression of microvascular disease and myocardial fibrosis in ESRD and that agents designed to restore normal aldosterone and NO homeostasis will improve microvascular and diastolic cardiac function in the heart of individuals with dialysis dependent ESRD. We will test 2 specific agents: The mineralocorticoid receptor blocker spironolactone; and L-arginine, an agent which improves NO bioavailability. Two specific aims will be addressed using a prospective, double-blinded, 2x2 factorial trial in dialysis dependent patients with ESRD. Subjects will be randomized to placebo, spironolactone plus placebo, L-arginine plus placebo, or combination spironolactone and L-arginine therapy. Diastolic cardiac function will be assessed using tissue Doppler index (TDI) determined mitral annular velocities (E') on LV echocardiography, and microvascular supply will be assessed using CFR-the ratio of hyperemic to resting myocardial blood flow-measured by positron emission tomography (PET) scans at baseline, 2 weeks and after 9 months of randomized therapy.

This randomized trial of spironolactone and L-arginine will provide important data about the contributions of aldosterone and NO to the pathogenesis of cardiovascular disease in ESRD, will demonstrate the therapeutic potential of L-arginine and spironolactone as as targeted cardiovascular therapies for use in ESRD, and will provide important insights into the underlying pathophysiology of cardiovascular disease in ESRD. The results generated will provide the data needed to design large-scale trials testing whether spironolactone or L-arginine can improve mortality or cardiovascular outcomes in ESRD.

Being tested
Spironolactone, L-arginine, Placebo
Keywords
Dialysis, ESRD, Cardiovascular disease, spironolactone, L-arginine, myocardial perfusion, coronary flow reserve, diastolic function
Medical subject headings
Kidney Failure, Chronic, Cardiovascular Diseases

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • SpironolactoneDrug

    Also called Aldactone

  • L-arginineDietary supplement

  • PlaceboDrug

Study groups in NCT01855334
Study groupRoleWhat they receive
Spironolactone + PlaceboExperimentalSpironolactone 25 mg by mouth daily + Placebo L-arginine-liquid formulation by mouth 3 times daily
Receives: Drug: Spironolactone; Drug: Placebo
Double PlaceboPlacebo comparatorPlacebo spironolactone-1 tablet by mouth daily + Placebo L-arginine liquid formulation by mouth 3 times daily
Receives: Drug: Placebo
Spironolactone + L-arginineExperimentalSpironolactone 25 mg daily + L-arginine 3 grams orally 3 times daily
Receives: Drug: Spironolactone; Dietary Supplement: L-arginine
L-arginine + PlaceboExperimentalL-arginine 3 grams by mouth 3 times daily + Placebo spironolactone 1 tablet by mouth daily
Receives: Dietary Supplement: L-arginine; Drug: Placebo

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Change in coronary Flow Reserve (PET)

    Coronary flow reserve will be measured using rest and stress 13N ammonia myocardial positron emission tomography (PET) at baseline and 9 months

    Measured: Between baseline and 9 months

  2. Change in left ventricular diastolic function

    Left ventricular diastolic function will be measured using mitral annular E' on tissue doppler index echocardiography at baseline and 9 months

    Measured: Between baseline and 9 months

Secondary outcomes (12)

  1. Association between coronary flow reserve (CFR) and tissue doppler index (E')

    Measured: Baseline

  2. Change in resting myocardial blood flow

    Measured: Between baseline and 9 months

  3. Change in left ventricular mass index

    Measured: Between baseline and 9 months

  4. Change in coronary vascular resistance

    Measured: Between 0 and 9 months

  5. Association between change in coronary flow reserve (CFR) and change in diastolic function-tissue doppler index (E')

    Measured: Between baseline and 9 months

  6. Change in early diastolic function (E')

    Measured: Between baseline and 2 weeks

  7. Combined cardiovascular safety

    Combined rate of death, myocardial infarction, stroke, or hospitalization

    Measured: Up to 9 months

  8. Cardiovascular death

    Measured: Up to 9 months

  9. Hyperkalemia

    Hyperkalemia requiring extra dialysis, adjustment in dialysate potassium, or discontinuation of therapy

    Measured: Up to 9 months

  10. Hypotension

    Symptomatic or intradialytic hypotension up to 9 months

    Measured: Up to 9 months

  11. Change in early coronary flow reserve

    Measured: Between baseline and 2 weeks

  12. Change in hyperemic myocardial blood flow

    Measured: Between baseline and 9 months

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted16 May 2013 (estimated)
  2. Study startSep 2013 (estimated)
  3. Primary completionJul 2018 (estimated)
  4. Study completionJul 2018 (estimated)

Why it stopped: change of funding leading to major redesign

Resources

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
Factorial
Masking
Quadruple blind
Who is masked
Participant, Care provider, Investigator, Outcomes assessor
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT01855334
Sponsor's protocol ID
1R01DK096189
Acronym
LAST-D
Status last verified
May 2017
First submitted
14 May 2013
Last updated
4 May 2017
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 33586138

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Spironolactone and L-arginine in people with End Stage Renal Disease and Hemodialysis, run by Brigham and Women's Hospital at 3 sites 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 2 inclusion and 17 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: withdrawn, as of the sponsor's last update on 4 May 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 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. Some participants in this study may receive a placebo. 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 withdrawn before enrolling participants, so there are no results.

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?

Change in coronary Flow Reserve (PET) (time frame: Between baseline and 9 months). The study lists 2 primary outcomes in all. 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 NCT01855334, 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 4 May 2017.

AzTrials uses cookies for analytics and advertising. You can accept or reject them; the site works either way. Privacy Policy.

Free account

Log in to keep searching

You’ve used your 3 free searches. AzTrials is free: log in or create a free account to keep searching clinical trials and save the ones you want to follow.

Create a free accountLog in