Kidney, PolycysticPhase 3HALT PKD BNCT01885559
HALT Progression of Polycystic Kidney Disease Study B
A Phase 3 study testing Lisinopril and Telmisartan in people with Kidney, Polycystic, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 7 sites in United States.
Trial summary
The efficacy of interruption of the renin-angiotensin-aldosterone system (RAAS) on the progression of cystic disease and on the decline in renal function in autosomal dominant kidney disease (ADPKD) will be assessed in two simultaneous multicenter randomized clinical trials targeting different levels of kidney… Read more about this study
- Who is it for?
- Ages 15 to 64 years
- Conditions the study is for
- Kidney, Polycystic
- What is being tested?
- Lisinopril and Telmisartan
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 486 participants
- Where
- 7 sitesUnited States
- Study dates
- Jan 2006to Jun 2014
- Phase
- Phase 3
- Are there results?
- Yes, posted in the registrySummary in the doctors' view
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 15 to 64 years
- All sexes
- No healthy volunteers
- Child, Adult
Who may be able to join
- Diagnosis of ADPKD.
- Age 15-49 (Study A); Age 18-64 (Study B).
- GFR >60 mL/min/1.73 m2 (Study A); GFR 25-60 mL/min/1.73 m2 (Study B).
- BP ≥130/80 or receiving treatment for hypertension.
- Informed Consent.
Who cannot join
- Pregnant/intention to become pregnant in 4-6 yrs.
- Documented renal vascular disease.
- Spot urine albumin-to-creatinine ratio of >0.5 (Study A) or ≥1.0 (Study B) and/or findings suggestive of kidney disease other than ADPKD.
- Diabetes requiring insulin or oral hypoglycemic agents / fasting serum glucose of >126 mg/dl / random non-fasting glucose of >200 mg/dl.
- Serum potassium >5.5 milliequivalent (mEq) /L for participants currently on ACE-I or ARB; >5.0 mEq/L for participants not currently on ACE-I or ARB.
- History of angioneurotic edema or other absolute contraindication for ACE-I or ARB. Intolerable cough associated with ACE-I is defined as a cough developing within six months of initiation of ACE-I in the absence of other causes and resolving upon discontinuation of the ACE-I.
Show all 17Show fewer
- Indication (other than hypertension) for β-blocker or calcium channel blocker therapy (e.g. angina, past myocardial infarction, arrhythmia), unless approved by the site principal investigator. (PI may choose to accept an individual who is on only a small dose of one of these agents and would otherwise be eligible.)
- Systemic illness necessitating nonsteroidal antiinflammatory drugs (NSAIDs), immunosuppressant or immunomodulatory medications.
- Systemic illness with renal involvement.
- Hospitalized for acute illness in past 2 months.
- Life expectancy <2 years.
- History of non-compliance.
- Unclipped cerebral aneurysm >7mm diameter.
- Creatine supplements within 3 months of screening visit.
- Congenital absence of a kidney (also total nephrectomy for Study B).
- Known allergy to sorbitol or sodium polystyrene sulfonate.
- Exclusions specific to magnetic resonance (MR) imaging (Study A).
Trial locations and contacts
7 sites in 1 country.
7 sites in 1 country
United States7 sites
Emory University School of Medicine
Atlanta, Georgia, 30322
University of Colorado Health Sciences Center
Aurora, Colorado, 800045
Tufts University-New England Medical Center
Boston, Massachusetts, 02111
Beth Israel Deaconess Medical Center
Boston, Massachusetts, 02215
Cleveland Clinic Foundation
Cleveland, Ohio, 44195
University of Kansas Medical Center
Kansas City, Kansas, 66160
Mayo Clinic
Rochester, Minnesota, 55905
About this study
The efficacy of interruption of the renin-angiotensin-aldosterone system (RAAS) on the progression of cystic disease and on the decline in renal function in autosomal dominant kidney disease (ADPKD) will be assessed in two simultaneous multicenter randomized clinical trials targeting different levels of kidney function: 1) early disease defined by GFR >60 mL/min/1.73 m2 (Study A); and 2) moderately advanced disease defined by GFR 25-60 mL/min/1.73 m2 (Study B). Participants will be recruited and enrolled, either to Study A or B, over the first three years. Participants enrolled in Study B will be followed for five-to-eight years, with the average length of follow-up being six and a half years.
Combination therapy will use angiotensin-converting-enzyme inhibitor (ACE-I) and an angiotensin-receptor blocker (ARB). Monotherapy will use ACE-I alone.
Read the detailed description
- Specific Aim of Study B
To study the effects of ACE-I/ARB combination therapy as compared to ACE-I monotherapy in the setting of standard blood pressure control (110-130/80 mm Hg) on the time to a 50% reduction of baseline estimated Glomerular Filtration Rate (eGFR), end-state renal disease (ESRD) or death, in hypertensive individuals with moderate renal insufficiency (GFR 25-60 mL/min/1.73m2).
- Hypothesis to be tested in Study B
In hypertensive ADPKD individuals with moderate renal insufficiency (GFR 25-60 mL/min/1.73 m2), intensive blockade of the RAAS using combination ACE-I/ARB therapy will slow the decline in kidney function over ACE-I monotherapy, independent of standard blood pressure control (110-130/80 mm Hg).
- Conditions
- Kidney, Polycystic
- Being tested
- Lisinopril, Telmisartan, Placebo
- Keywords
- polycystic kidney disease, polycystic, kidney, disease, adpkd, halt, pkd, blood pressure, bp, hypertension, renal, renin-angiotensin-aldosterone-system, RAAS
- Medical subject headings
- Polycystic Kidney Diseases, Disease, Polycystic Kidney, Autosomal Dominant, Familial paroxysmal dystonia, Hypertension
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
LisinoprilDrug
Also called ACE-I, ACE, Ace-Inhibitor
Lisinopril titrated to 5mg, 10mg, 20mg, 40mg as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg.
TelmisartanDrug
Also called ARB
Telmisartan titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg.
PlaceboDrug
Also called Control
Placebo titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg.
| Study group | Role | What they receive |
|---|---|---|
| ACE-I + placebo | Placebo comparator | Monotherapy of lisinopril and placebo. Standard blood pressure control of 110-130/80 mm Hg Receives: Drug: Lisinopril; Drug: Placebo |
| ACE-I + ARB | Active comparator | Dual therapy of lisinopril and telmisartan treatments. Standard blood pressure control of 110-130/80 mm Hg. Receives: Drug: Lisinopril; Drug: Telmisartan |
What is being measured
The primary outcome is the main question the study is designed to answer.
Number of Participants With 50% Reduction of Baseline eGFR, End Stage Renal Disease (ESRD, Initiation of Dialysis or Preemptive Transplant), or Death.
Measured: Patients followed for 5-8 years with average of 6.5 years follow up
Secondary outcomes (7)
Albuminuria
Annual percent change in 24 hour urine albumin, centrally processed. Data from multiple years were analyzed with the primary focus on the change over time for the measure (from the slope of the model). The measure presented is the average annual percent change across the 8 years.
Measured: up to 8 years (annually assessed)
Aldosterone
Annual percent change in urinary aldosterone, centrally processed measure. Data from multiple years were analyzed with the primary focus on the change over time for the measure (from the slope for time from the model). The measure presented is the average annual percent change across the 8 years.
Measured: up at 8 years (annually assessed)
Hospitalizations
Hospitalization for any cause
Measured: up to 8 years
Cardiovascular Hospitalizations
Cause-specific hospitalizations (cardiovascular)
Measured: up to 8 years
Quality of Life Physical Component Summary
Short Form-36 Quality of Life Physical Component Summary ranges from 0 (worst possible outcome) to 100 (best possible outcome). Data from multiple years were analyzed with the primary focus on the change over time for the measure (from the slope for time from the model). The measure presented is the average annual change across the 8 years.
Measured: up to 8 years (annually assessed)
Quality of Life Mental Component Summary
Short Form-36 Quality of Life Mental Component Summary ranges from 0 (worst possible outcome) to 100 (best possible outcome). Data from multiple years were analyzed with the primary focus on the change over time for the measure (from the slope for time from the model). The measure presented is the average annual change across the 8 years.
Measured: up to 8 years (annually assessed)
Back or Flank Pain
Report of back or flank pain since the last visit (yes or no)
Measured: 48 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted25 Jun 2013 (estimated)
- Study startJan 2006
- Primary completionJun 2014
- Study completionJun 2014
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Posted resultsParticipant flow, outcome measures and adverse events reported by the sponsor.
- Publications (3)Papers the sponsor has linked to this study.
- Other trials for Kidney, PolycysticStudies of the same condition, open and under way.
- More trials run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)The sponsor's other registered studies.
- 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 3
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 486 participants (actual)
Sponsor and investigators
- Sponsor type
- US National Institutes of Health
- Collaborators
- Boehringer Ingelheim, Merck Sharp & Dohme LLC, Polycystic Kidney Disease Foundation, University of Pittsburgh, Washington University School of Medicine
- Responsible party
- Sponsor
- Investigators
- Robert Schrier, M.D., Study chair, University of Colorado, DenverArlene Chapman, M.D., Principal investigator, Emory UniversityRonald Perrone, M.D., Principal investigator, Tufts University-New England Medical CenterVicente Torres, M.D., Principal investigator, Mayo ClinicMarva Moxey-Mims, M.D., Study director, National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)Charity G Moore, PhD, Principal investigator, University of Pittsburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01885559
- Sponsor's protocol ID
- HALT PKD B
- Other IDs
- U01DK062401, U01DK082230
- Acronym
- HALT PKD B
- Status last verified
- Apr 2020
- First submitted
- 17 Jun 2013
- Last updated
- 22 Apr 2020
- Results posted
- Yes, on ClinicalTrials.gov
- Data monitoring committee
- Yes
- FDA-regulated drug
- Yes
- FDA-regulated device
- No
- Individual data sharing
- Yes: Data are available at the NIDDK Central Repository, https://repository.niddk.nih.gov/studies/halt-pkd/?query=halt%20pkd
Publications
St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
PubMed 39356039Chebib FT, Zhou X, Garbinsky D, Davenport E, Nunna S, Oberdhan D, Fernandes A. Tolvaptan and Kidney Function Decline in Older Individuals With Autosomal Dominant Polycystic Kidney Disease: A Pooled Analysis of Randomized Clinical Trials and Observational Studies. Kidney Med. 2023 Apr 14;5(6):100639. doi: 10.1016/j.xkme.2023.100639. eCollection 2023 Jun.
PubMed 37250503Torres VE, Abebe KZ, Chapman AB, Schrier RW, Braun WE, Steinman TI, Winklhofer FT, Brosnahan G, Czarnecki PG, Hogan MC, Miskulin DC, Rahbari-Oskoui FF, Grantham JJ, Harris PC, Flessner MF, Moore CG, Perrone RD; HALT-PKD Trial Investigators. Angiotensin blockade in late autosomal dominant polycystic kidney disease. N Engl J Med. 2014 Dec 11;371(24):2267-76. doi: 10.1056/NEJMoa1402686. Epub 2014 Nov 15.
PubMed 25399731
Study at a glance
From the registry record, last updated by the sponsor on 22 Apr 2020. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- HALT Progression of Polycystic Kidney Disease Study B
- ClinicalTrials.gov ID
- NCT01885559
- Acronym / sponsor ID
- HALT PKD B / HALT PKD B
- Conditions
- Kidney, Polycystic
- Keywords
- polycystic kidney disease, polycystic, kidney, disease, adpkd, halt, pkd, blood pressure
- Phase
- Phase 3
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 486 participants (actual)
- Lead sponsor
- National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)US National Institutes of Health
- Collaborators
- Boehringer Ingelheim, Merck Sharp & Dohme LLC, Polycystic Kidney Disease Foundation, University of Pittsburgh, Washington University School of Medicine
- Study start
- Jan 2006 (actual)
- Primary completion
- Jun 2014 (actual)
- Study completion
- Jun 2014 (actual)
- First posted
- 25 Jun 2013 (estimated)
- Results
- Posted 10 Mar 2015
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
The efficacy of interruption of the renin-angiotensin-aldosterone system (RAAS) on the progression of cystic disease and on the decline in renal function in autosomal dominant kidney disease (ADPKD) will be assessed in two simultaneous multicenter randomized clinical trials targeting different levels of kidney function: 1) early disease defined by GFR >60 mL/min/1.73 m2 (Study A); and 2) moderately advanced disease defined by GFR 25-60 mL/min/1.73 m2 (Study B). Participants will be recruited and enrolled, either to Study A or B, over the first three years. Participants enrolled in Study B will be followed for five-to-eight years, with the average length of follow-up being six and a half years.
Combination therapy will use angiotensin-converting-enzyme inhibitor (ACE-I) and an angiotensin-receptor blocker (ARB). Monotherapy will use ACE-I alone.
Detailed description
- Specific Aim of Study B
To study the effects of ACE-I/ARB combination therapy as compared to ACE-I monotherapy in the setting of standard blood pressure control (110-130/80 mm Hg) on the time to a 50% reduction of baseline estimated Glomerular Filtration Rate (eGFR), end-state renal disease (ESRD) or death, in hypertensive individuals with moderate renal insufficiency (GFR 25-60 mL/min/1.73m2).
- Hypothesis to be tested in Study B
In hypertensive ADPKD individuals with moderate renal insufficiency (GFR 25-60 mL/min/1.73 m2), intensive blockade of the RAAS using combination ACE-I/ARB therapy will slow the decline in kidney function over ACE-I monotherapy, independent of standard blood pressure control (110-130/80 mm Hg).
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| ACE-I + placebo | Placebo comparator | Drug: Lisinopril, Drug: PlaceboMonotherapy of lisinopril and placebo. Standard blood pressure control of 110-130/80 mm Hg |
| ACE-I + ARB | Active comparator | Drug: Lisinopril, Drug: TelmisartanDual therapy of lisinopril and telmisartan treatments. Standard blood pressure control of 110-130/80 mm Hg. |
Who may qualify
- Ages
- 15 to 64 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult
Key inclusion criteria (5 listed)
- Diagnosis of ADPKD.
- Age 15-49 (Study A); Age 18-64 (Study B).
- GFR >60 mL/min/1.73 m2 (Study A); GFR 25-60 mL/min/1.73 m2 (Study B).
- BP ≥130/80 or receiving treatment for hypertension.
- Informed Consent.
Key exclusion criteria (17 listed)
- Pregnant/intention to become pregnant in 4-6 yrs.
- Documented renal vascular disease.
- Spot urine albumin-to-creatinine ratio of >0.5 (Study A) or ≥1.0 (Study B) and/or findings suggestive of kidney disease other than ADPKD.
- Diabetes requiring insulin or oral hypoglycemic agents / fasting serum glucose of >126 mg/dl / random non-fasting glucose of >200 mg/dl.
- Serum potassium >5.5 milliequivalent (mEq) /L for participants currently on ACE-I or ARB; >5.0 mEq/L for participants not currently on ACE-I or ARB.
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 |
|---|---|---|
| LisinoprilAlso: ACE-I, ACE, Ace-InhibitorLisinopril titrated to 5mg, 10mg, 20mg, 40mg as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg. | Drug | ACE-I + ARB, ACE-I + placebo |
| TelmisartanAlso: ARBTelmisartan titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg. | Drug | ACE-I + ARB |
| PlaceboAlso: ControlPlacebo titrated to 40mg and 80mg, as tolerated by participants, to achieve standard blood pressure control of 110-130/80 mm Hg. | Drug | ACE-I + placebo |
Primary outcome
Number of Participants With 50% Reduction of Baseline eGFR, End Stage Renal Disease (ESRD, Initiation of Dialysis or Preemptive Transplant), or Death.
Time frame: Patients followed for 5-8 years with average of 6.5 years follow up
7 secondary outcomes
Albuminuria
Time frame: up to 8 years (annually assessed)
Aldosterone
Time frame: up at 8 years (annually assessed)
Hospitalizations
Time frame: up to 8 years
Cardiovascular Hospitalizations
Time frame: up to 8 years
Quality of Life Physical Component Summary
Time frame: up to 8 years (annually assessed)
Quality of Life Mental Component Summary
Time frame: up to 8 years (annually assessed)
Back or Flank Pain
Time frame: 48 months
Results and safety
Loading the posted results from ClinicalTrials.gov…
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 22 Apr 2020.
- Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
- Derived from this study: PubMed 39356039St Pierre K, Cashmore BA, Bolignano D, Zoccali C, Ruospo M, Craig JC, Strippoli GF, Mallett AJ, Green SC, Tunnicliffe DJ. Interventions for preventing the progression of autosomal dominant polycystic kidney disease. Cochrane Database Syst Rev. 2024 Oct 2;10(10):CD010294. doi: 10.1002/14651858.CD010294.pub3.
- Derived from this study: PubMed 37250503Chebib FT, Zhou X, Garbinsky D, Davenport E, Nunna S, Oberdhan D, Fernandes A. Tolvaptan and Kidney Function Decline in Older Individuals With Autosomal Dominant Polycystic Kidney Disease: A Pooled Analysis of Randomized Clinical Trials and Observational Studies. Kidney Med. 2023 Apr 14;5(6):100639. doi: 10.1016/j.xkme.2023.100639. eCollection 2023 Jun.
- Derived from this study: PubMed 25399731Torres VE, Abebe KZ, Chapman AB, Schrier RW, Braun WE, Steinman TI, Winklhofer FT, Brosnahan G, Czarnecki PG, Hogan MC, Miskulin DC, Rahbari-Oskoui FF, Grantham JJ, Harris PC, Flessner MF, Moore CG, Perrone RD; HALT-PKD Trial Investigators. Angiotensin blockade in late autosomal dominant polycystic kidney disease. N Engl J Med. 2014 Dec 11;371(24):2267-76. doi: 10.1056/NEJMoa1402686. Epub 2014 Nov 15.
- Polycystic Kidney Disease Foundation WebsiteLink provided by the sponsor.
- Individual participant dataSharing planned: Yes. Data are available at the NIDDK Central Repository, https://repository.niddk.nih.gov/studies/halt-pkd/?query=halt%20pkd
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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.
Robert Schrier, M.D. study chair
University of Colorado, Denver
Arlene Chapman, M.D. principal investigator
Emory University
Ronald Perrone, M.D. principal investigator
Tufts University-New England Medical Center
7 sites in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 3 study testing Lisinopril and Telmisartan in people with Kidney, Polycystic, run by National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK) at 7 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 5 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: finished, as of the sponsor's last update on 22 Apr 2020. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 7 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 3 studies compare the treatment with the current standard treatment or a placebo in a large group, to confirm how well it works and watch for side effects.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Yes. Results are posted in the registry (first posted 10 Mar 2015). A summary is in the For doctors view, and the full results are on ClinicalTrials.gov.
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?
Number of Participants With 50% Reduction of Baseline eGFR, End Stage Renal Disease (ESRD, Initiation of Dialysis or Preemptive Transplant), or Death. (time frame: Patients followed for 5-8 years with average of 6.5 years follow up). 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 NCT01885559, which also lists 3 linked publications.
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 22 Apr 2020.