Renal Insufficiency, ChronicPhase 4MRA-ACENCT03502031
Safety and Efficacy of Two Year of RAAS Alone or in Combination With Spironolactone Therapy
A Phase 4 study testing Renin-Angiotensin (RAAS) alone and Renin-Angiotensin (RAAS) blockers in combination with Spironolactone in people with Renal Insufficiency, Chronic and Diabetic Nephropathy Type 2, run by James A. Tumlin, MD at 2 sites in United States.
Trial summary
NephroNet proposes to examine whether combining Spironolactone with maximal RAAS blockade will further reduce urinary protein at one year and whether prolonged therapy (24 months) is able to slow the decline in GFR. Read more about this study
- Who is it for?
- Ages 75 years and older
- Conditions the study is for
- Renal Insufficiency, Chronic, Diabetic Nephropathy Type 2
- What is being tested?
- Renin-Angiotensin (RAAS) alone and Renin-Angiotensin (RAAS) blockers in combination with Spironolactone
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 72 participants
- Where
- 2 sitesUnited States
- Study dates
- 1 Oct 2018to 1 Oct 2024
- 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 75 years and older
- All sexes
- No healthy volunteers
- Older adult
Who may be able to join
- Age above 18
- Male or Female
- Patients with Type II diabetes mellitus must be receiving oral agents or insulin injections at the time of randomization
- All eligible patients will be on a stable, maximum to dose of an ACE or ARB for 2 weeks prior to randomization.
- Note: The determination of m tolerated ACE-ARB therapy will be left to the discretion of the site princ
- All eligible patientswill have hypertension targetblood pressur of < 140/90mm Hg.
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- Antihypertensiv therapy may be adjusted to achieve the target blood pressure prior to the time of randomization.
- ACE or ARB therapy will be the primary antihypertensive therapy used for blood pressure control and will be titrthe highest tolerated dose to achieve a target blood pressure of <Patients requiring additional medications to achieve the target blood pressure will use antihypertensive agents that have neutral effects on urinary proteinuria (e.g. Hydralazine or lo Dihydropyridine calcium channel blockers etc.). CcThe final choice of additional medications will be left to the discretion of the site principal investigator (PI)
- Patients with anurine protein to creatinine (UP/Cr) ratio that is mg/gm from the average of two historical value within one year prior to randomization will be considered eligible for study entry.
- Patients with a baseline K+ of >5. X5 meq/l on maximum tolerated ACE-ARB therapy during the screening period can be treated with 8.4 grams of Patiromer for 7 days. If at the end of 7days the serum K+ is < 5.0 meq/liter the patient will be considered eligible to participate in the study. If at the end of 7 days the serum K+ >5.0 meq/l the dose of Patiromer can be increased to 16.8 grams. If at the end of 7 days the serum K+ is < 5.0 meq/L, the patient will be considered eligible for study entry. If after 7 days at the higher dose of Patiromer the serum K+ >5.0, the patient will be ineligible for study participation.
- Patients with an estimated GFR by CK-Epi .73 m2
- Female patients will be required to undergo routine birth control measures
Who cannot join
- Estimated GFR by MDRD20 mls/min/1.73 M2 using the CKD-Epi equation
- Patients with serum K+ > 5.00 while taking 16.8/day of Patiromer
- Patients with history of Type mellitus
- Patients with HgbA
- Pregnant or breast-feeding female patients
- Female patients unwilling to receive estrogen or progesterone based birth control or are unwilling or unable to usconventional barrier birth control methods.
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- Patients with known allergy or intolerance tor Spironolactone therapy
- Patients taking oral or IV digoxin
- Patients receiving chronic steroids > 1oral Prednisone
- Patient that do nohave minimum o eGFR determinations within 2 years prior to study randomization
- Concurrent use of Amiloride, , Aliskerin, or other Aldosterone antagonists Patien receiving any of the above medications will be considered eligible for study participation after a wash-out
Trial locations and contacts
2 sites in 1 country.
United States2 sites, 2 recruiting
- Recruiting
Nelson Kopyt, MD
Bethlehem, Pennsylvania, 18017
Stephanie Hanzl, 610-433-4100 ext. 490, shanzl@necresearch.org
- Recruiting
Georgia Nephrology Research Institute
Lawrenceville, Georgia, 30046
James A Tumlin, MD, 770-490-9203, jamestumlinmdnephronet@gmail.com
Jeremy Whitson, CCRA, 423-943-4265, jwhitson@nephro-synergy.com
About this study
Official title: Safety and Efficacy of Maximally Tolerated RAAS Blockade and Spironolactone Therapy on Urinary Proteinuria and Progression of Type II Diabetic Nephropathy in African Americans and Other Patient Cohorts.
NephroNet proposes to examine whether combining Spironolactone with maximal RAAS blockade will further reduce urinary protein at one year and whether prolonged therapy (24 months) is able to slow the decline in GFR. Because of combination MRA and RAAS therapy significantly increases the risk for clinically significant hyperkalemia, we also plan to determine whether the addition of Patiromer to these patients facilitates the use of combination therapy and allows a larger proportion of diabetic patients the potential benefit of combination therapy on renal function.
- Being tested
- Renin-Angiotensin (RAAS) alone, Renin-Angiotensin (RAAS) blockers in combination with Spironolactone
- Medical subject headings
- Renal Insufficiency, Chronic
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Renin-Angiotensin (RAAS) aloneDrug
Also called Lispril, Enalapril, Perindopril, Losarta, Valsar etc.,
maximal RAAS blockade alone for 24months.
Renin-Angiotensin (RAAS) blockers in combination with SpironolactoneDrug
Also called Lisinopril, Enalapril, Perindopril, Losartan, Valsartan, or Spironolactone
maximal RAAS blockade alone or in combination with Spironolactone (25 mg) for 24 months.
| Study group | Role | What they receive |
|---|---|---|
| RAAS alone | Active comparator | RAAS (Lisinopril, Enalapril, Perindopril, Losartan, and Valsartan taken each day at maximum tolerated dose that will different for each subject) Receives: Drug: Renin-Angiotensin (RAAS) alone |
| RAAS in Combination with Spironolactone | Active comparator | RAAS (Lisinopril, Enalapril, Perindopril, Losartan, and Valsartan taken each day at maximum tolerated dose that will different for each subject); Spironolactone taken each day at 25mg Receives: Drug: Renin-Angiotensin (RAAS) blockers in combination with Spironolactone |
What is being measured
The primary outcome is the main question the study is designed to answer.
Combination Therapy - RAAS inhibition and Spironolactone to lower UP/Cr
To determine whether combination therapy with maximall RAAS inhibition and Spironolactone is superior to RAAS inhibition alone in lowering the UP/Cr ratio at 12 months
Measured: 24 months
Secondary outcomes (2)
Combination Therapy - RAAS inhibition and Spironolactone
To determine whether combination therapy with maximally tolerated RAAS inhibition and Spironolactone is superior to RAAS inhibition alone in slowing the progression of renal disease as evidenced by changes in GFR
Measured: 24 months
Combination Therapy - RAAS inhibition and Spironolactone that develop hyperkalemia
To determine the patients in the maximal RAAS blockade group and those receiving combination RAAS + Spironolactone therapy developing clinically significant hyperkalemia as defined as a serum K+ level greater than 5.5 meq/L. We will determine the percentage of patients that require "Patiromer-Rescue" for K+ > 5.5 meq/L and the percentage of patients maintained with serum K+ less than 5.5 meq/L
Measured: 12 months, 24 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Apr 2018
- Study start1 Oct 2018
- Primary completion1 Oct 2022
- Study completion1 Oct 2024 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Renal Insufficiency, ChronicStudies 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
- None (open label)
- Enrolment
- 72 participants (estimated)
Sponsor and investigators
- Lead sponsor
- James A. Tumlin, MD
- Sponsor type
- University, hospital or other
- Collaborators
- Nelson Kopyt, MD
- Responsible party
- Sponsor-investigator, James A. Tumlin, MD, NephroNet, Inc.
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03502031
- Sponsor's protocol ID
- NN-01
- Acronym
- MRA-ACE
- Status last verified
- Oct 2022
- First submitted
- 13 Nov 2017
- Last updated
- 28 Oct 2022
- Results posted
- No
- Data monitoring committee
- No
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 28 Oct 2022. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Safety and Efficacy of Maximally Tolerated RAAS Blockade and Spironolactone Therapy on Urinary Proteinuria and Progression of Type II Diabetic Nephropathy in African Americans and Other Patient Cohorts.
- ClinicalTrials.gov ID
- NCT03502031
- Acronym / sponsor ID
- MRA-ACE / NN-01
- Phase
- Phase 4
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 72 participants (estimated)
- Lead sponsor
- James A. Tumlin, MDUniversity, hospital or other
- Collaborators
- Nelson Kopyt, MD
- Study start
- 1 Oct 2018 (actual)
- Primary completion
- 1 Oct 2022 (actual)
- Study completion
- 1 Oct 2024 (estimated)
- First posted
- 18 Apr 2018 (actual)
- 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.
NephroNet proposes to examine whether combining Spironolactone with maximal RAAS blockade will further reduce urinary protein at one year and whether prolonged therapy (24 months) is able to slow the decline in GFR. Because of combination MRA and RAAS therapy significantly increases the risk for clinically significant hyperkalemia, we also plan to determine whether the addition of Patiromer to these patients facilitates the use of combination therapy and allows a larger proportion of diabetic patients the potential benefit of combination therapy on renal function.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| RAAS alone | Active comparator | Drug: Renin-Angiotensin (RAAS) aloneRAAS (Lisinopril, Enalapril, Perindopril, Losartan, and Valsartan taken each day at maximum tolerated dose that will different for each subject) |
| RAAS in Combination with Spironolactone | Active comparator | Drug: Renin-Angiotensin (RAAS) blockers in combination with SpironolactoneRAAS (Lisinopril, Enalapril, Perindopril, Losartan, and Valsartan taken each day at maximum tolerated dose that will different for each subject); Spironolactone taken each day at 25mg |
Who may qualify
- Ages
- 75 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Older adult
Key inclusion criteria (12 listed)
- Age above 18
- Male or Female
- Patients with Type II diabetes mellitus must be receiving oral agents or insulin injections at the time of randomization
- All eligible patients will be on a stable, maximum to dose of an ACE or ARB for 2 weeks prior to randomization.
- Note: The determination of m tolerated ACE-ARB therapy will be left to the discretion of the site princ
Key exclusion criteria (11 listed)
- Estimated GFR by MDRD20 mls/min/1.73 M2 using the CKD-Epi equation
- Patients with serum K+ > 5.00 while taking 16.8/day of Patiromer
- Patients with history of Type mellitus
- Patients with HgbA
- Pregnant or breast-feeding female patients
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 |
|---|---|---|
| Renin-Angiotensin (RAAS) aloneAlso: Lispril, Enalapril, Perindopril, Losarta, Valsar etc.,maximal RAAS blockade alone for 24months. | Drug | RAAS alone |
| Renin-Angiotensin (RAAS) blockers in combination with SpironolactoneAlso: Lisinopril, Enalapril, Perindopril, Losartan, Valsartan, or Spironolactonemaximal RAAS blockade alone or in combination with Spironolactone (25 mg) for 24 months. | Drug | RAAS in Combination with Spironolactone |
Primary outcome
Combination Therapy - RAAS inhibition and Spironolactone to lower UP/Cr
Time frame: 24 months
To determine whether combination therapy with maximall RAAS inhibition and Spironolactone is superior to RAAS inhibition alone in lowering the UP/Cr ratio at 12 months
2 secondary outcomes
Combination Therapy - RAAS inhibition and Spironolactone
Time frame: 24 months
Combination Therapy - RAAS inhibition and Spironolactone that develop hyperkalemia
Time frame: 12 months, 24 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 28 Oct 2022.
- Individual participant dataSharing planned: No
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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.
2 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 Renin-Angiotensin (RAAS) alone and Renin-Angiotensin (RAAS) blockers in combination with Spironolactone in people with Renal Insufficiency, Chronic and Diabetic Nephropathy Type 2, run by James A. Tumlin, MD at 2 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 12 inclusion and 11 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: status not confirmed, as of the sponsor's last update on 28 Oct 2022. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 2 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. 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?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact James A Tumlin, MD (770-490-9203, jamestumlinmdnephronet@gmail.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Combination Therapy - RAAS inhibition and Spironolactone to lower UP/Cr (time frame: 24 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
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 28 Oct 2022.