Chronic Hemodialysis (ESRD)Phase 4HIDENCT02228408

Safety and Cardiovascular Efficacy of Hydralazine and Isosorbide Dinitrate in Dialysis-Dependent ESRD

A Phase 4 study testing Hydralazine/Isorsorbide Dinitrate in people with Chronic Hemodialysis (ESRD), run by Brigham and Women's Hospital at 1 site in United States.

Completed

Finished. The study has ended and is not enrolling. Results may be posted on the official record.

Official record

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Trial summary

This study is a pilot study designed to compare the safety and cardiovascular effects of 26 weeks of combination hydralazine/isorsorbide dinitrate therapy with placebo therapy in patients receiving chronic hemodialysis. Read more about this study

Who is it for?: Ages 18 to 85 years
Conditions the study is for: Chronic Hemodialysis (ESRD)
What is being tested?: Hydralazine/Isorsorbide Dinitrate
Could I receive a placebo?: Yes, some participants may receive a placebo
How many people: 17 participants
Where: 1 siteUnited States
Study dates: 28 Aug 2017to 7 May 2019
Phase: Phase 4
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 18 to 85 years
All sexes
No healthy volunteers
Adult, Older adult

Who may be able to join

Maintenance hemodialysis therapy for end-stage renal disease
Age 18-85 years
≥ 90 days since dialysis initiation
Ability to provide informed consent
Pre-dialysis seated systolic blood pressure measurements must be ≥ 120 mm Hg in the 2 weeks before enrollment and on the day of randomization.

Who cannot join

Serum potassium ≥6.5 mEq/L within 2 months prior to screening
Unscheduled dialysis for hyperkalemia within the 3 months prior to screening
Hypotension defined as pre-dialysis SBP <100 mm Hg (seated measurement) within 4 weeks prior to enrollment
Recurrent intra-dialytic hypotension, defined as systolic blood pressure <80 mm Hg during ≥3 dialysis sessions per 30-day rolling period or treatment for either hypotension or symptoms of hypotension if systolic blood pressure is < 100 mm Hg during ≥3 dialysis sessions per 30-day rolling period.
Mitral valve repair or replacement
Severe mitral valve disease by echocardiography, coronary angiography or cardiac magnetic resonance imaging

Show all 21Show fewer

Prior coronary artery bypass graft
Anticipated kidney transplant, change to peritoneal dialysis, or transfer to another dialysis unit within 6 months
Expected survival < 6 months
Allergy to study medications (ISD, HY, adenosine/diprimidole)
Active use of sildenafil, vardenafil or tadalafil
History of severe aortic stenosis or other cause of LV outflow obstruction
Pregnancy, anticipated pregnancy, or breastfeeding, confirmed by serum pregnancy test on the day of PET scan
Incarceration
Participation in another intervention study
Use of monoamine oxidase inhibitors
Contraindication to adenosine including
2nd or 3rd degree heart block, sick sinus syndrome or symptomatic bradycardia (without a functioning pacemaker)
moderate or severe asthma
chronic obstructive pulmonary disease
Active use of any of the study medications unless participant and physician willing to discontinue prior to enrollment.

Trial locations and contacts

1 site in 1 country.

United States1 site

Brigham & Women's Hospital
Boston, Massachusetts, 02115

Other trials in United States

About this study

Official title: A Phase IV Randomized, Double-blind, Active-controlled, Single-center Study of the Safety and Effects on Cardiac Structure and Function of Hydralazine and Isosorbide Dinitrate in Patients With Hemodialysis Dependent ESRD

The investigators hypothesize that treatment of chronic hemodialysis (ESRD) patients with a combination of hydralazine/isosorbide dinitrate compared with placebo is safe and that it will improve heart function as well blood flow/blood vessel supply.

Read the detailed description

Sixteen patients receiving maintenance hemodialysis will be randomized to 26 weeks of therapy with combination hydralazine/isosorbide dinitrate or placebo. Study medications will be titrated to goal dose during the first 4 weeks and maintained at goal dose (as tolerated) between weeks 4-26. A final study visit to assess symptoms after drug discontinuation will occur 4 weeks after drug discontinuation.

Study duration-Maximum of 32 weeks with 26 weeks of active therapy.

Efficacy Measures -Tissue Doppler echocardiography and myocardial perfusion scanning using radioactive NH3 PET will be assessed at weeks 0 and 26.

Safety Measures-Adverse events rates including inter- and intra-dialytic hypotension, ,cardiovascular death and gastrointestinal symptoms will be assessed throughout the duration of the study.

Conditions: Chronic Hemodialysis (ESRD)
Being tested: Hydralazine/Isorsorbide Dinitrate, Placebo
Keywords: hemodialysis, ESRD, Cardiovascular Disease, Isosorbide Dinitrate, Hydralazine
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.

Hydralazine/Isorsorbide DinitrateDrug
Also called Apresoline, Isordil
Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.
Target Dose:
Hydralazine 75 mg 3x day Isorsorbide Dintrate 40 mg 3x/day
Allowable Dosage Forms:
ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35 mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Dose Titration:
ISD/HY will be administered at a starting dose ISD/HY 10 mg/10-3x/day and titrated to ISD/HY 20 mg/35 mg-3x/day after 4 days and to ISD/HY 40 mg/75 mg-3x/day at 4 weeks. Dose will be decreased as necessary for dose-limiting side effects.
PlaceboDrug
Placebo titration will mimic titration of active study arm

Study groups in NCT02228408
Study group	Role	What they receive
Hydralazine/Isorsorbide Dinitrate	Experimental	Hydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events. Allowable Dosage Forms: ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35mg-3x/day ISD/HY 40 mg/75 mg-3x/day Receives: Drug: Hydralazine/Isorsorbide Dinitrate
Placebo	Active comparator	Placebo will be administered Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events. Receives: Drug: Placebo

What is being measured

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

Rate of Hypotension, Serious Adverse Events, GI Events and Cardiovascular Death
Rate of primary Safety Outcomes(hypotension, serious adverse events, GI events and CV death)
Measured: 6 months
Efficacy-Change in Coronary Flow Reserve (CFR) From 0-6 Months
Primary Efficacy Measure-CFR measured on rest and stress Positron Emission Tomography
Measured: 0 to 6 months
Change in E' on TDI Echo From 0-6 Months
Co-primary efficacy measure measured on Tissue Doppler Echocardiography
Measured: 0 to 6 months
Reduction in Drug Dose or Discontinuation of Study Drug
Primary Tolerability measure
Measured: 0 to 6 months
Number of Patients Completing Study From 0 to 6 Months
Primary Feasibility Measure
Measured: 0 to 6 months

Secondary outcomes (2)

Change in Circulating Fibrosis Markers and Angiogenesis Markers
Circulating concentrations of markers such as the carboxy terminal of pro-collagen type 1 or ADMA will be measured
Measured: 0 to 6 months
Change in LVMI
Change in left ventricular mass index between baseline and 6 months.
Measured: 0 to 6 months

Timeline

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

28 Aug 20177 May 2019

First posted29 Aug 2014 (estimated)
Study start28 Aug 2017
Primary completion7 May 2019
Study completion7 May 2019

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 (1)Papers the sponsor has linked to this study.
Other trials for Chronic Hemodialysis (ESRD)Studies of the same condition, open and under way.
More trials run by Brigham and Women's HospitalThe 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 4
Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind
Who is masked: Participant, Care provider, Investigator, Outcomes assessor
Enrolment: 17 participants (actual)

IDs, dates and publications

ClinicalTrials.gov ID: NCT02228408
Sponsor's protocol ID: DK100772-01
Acronym: HIDE
Status last verified: Mar 2021
First submitted: 26 Aug 2014
Last updated: 27 Apr 2021
Results posted: Yes, on ClinicalTrials.gov
Data monitoring committee: Yes
FDA-regulated drug: Yes
FDA-regulated device: No
Individual data sharing: Yes: deidentified may be shared upon request to the PI

Publications

Mugendi GA, Mutua FM, Natale P, Esterhuizen TM, Strippoli GF. Calcium channel blockers for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev. 2020 Oct 1;10(10):CD011064. doi: 10.1002/14651858.CD011064.pub2.
PubMed 33000470

Want to know more?

The sponsor has not listed a contact. The official record may have more details.

Talk to your doctor first and take this page with you. Only the study team can confirm whether you can join.

Questions to ask the study team

What is the study trying to find out?
What would I need to do, and how often would I visit?
Could I receive a placebo instead of the treatment?
What are the possible risks and benefits for me?
Will it cost me anything? Are travel or time paid for?
Can I keep seeing my own doctor during the study?
What happens when the study ends?

See locations

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All Chronic Hemodialysis (ESRD) trials

Study at a glance

From the registry record, last updated by the sponsor on 27 Apr 2021. Recruitment status is as the sponsor reported it: confirm with the study team.

Official title: A Phase IV Randomized, Double-blind, Active-controlled, Single-center Study of the Safety and Effects on Cardiac Structure and Function of Hydralazine and Isosorbide Dinitrate in Patients With Hemodialysis Dependent ESRD
ClinicalTrials.gov ID: NCT02228408
Acronym / sponsor ID: HIDE / DK100772-01
Conditions: Chronic Hemodialysis (ESRD)
Keywords: hemodialysis, ESRD, Cardiovascular Disease, Isosorbide Dinitrate, Hydralazine
Phase: Phase 4
Study type: Interventional
Recruitment status: Completed
Enrolment: 17 participants (actual)
Lead sponsor: Brigham and Women's HospitalUniversity, hospital or other
Study start: 28 Aug 2017 (actual)
Primary completion: 7 May 2019 (actual)
Study completion: 7 May 2019 (actual)
First posted: 29 Aug 2014 (estimated)
Results: Posted 27 Apr 2021

Clinical summary

The research question as the sponsor registered it. This describes what the study plans to test, not what it found.

Detailed description

Study duration-Maximum of 32 weeks with 26 weeks of active therapy.

Efficacy Measures -Tissue Doppler echocardiography and myocardial perfusion scanning using radioactive NH3 PET will be assessed at weeks 0 and 26.

Safety Measures-Adverse events rates including inter- and intra-dialytic hypotension, ,cardiovascular death and gastrointestinal symptoms will be assessed throughout the duration of the study.

Study design

Primary purpose: Prevention
Allocation: Randomised
Intervention model: Parallel groups
Masking: Quadruple blind (participant, care provider, investigator, outcomes assessor)
Number of arms: 2

Arm	Type	Receives
Hydralazine/Isorsorbide Dinitrate	Experimental	Drug: Hydralazine/Isorsorbide DinitrateHydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events. Allowable Dosage Forms: ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35mg-3x/day ISD/HY 40 mg/75 mg-3x/day
Placebo	Active comparator	Drug: PlaceboPlacebo will be administered Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events.

Who may qualify

Ages: 18 to 85 years
Sex: All
Healthy volunteers: Not accepted
Age groups: Adult, Older adult

Key inclusion criteria (5 listed)

Maintenance hemodialysis therapy for end-stage renal disease
Age 18-85 years
≥ 90 days since dialysis initiation
Ability to provide informed consent
Pre-dialysis seated systolic blood pressure measurements must be ≥ 120 mm Hg in the 2 weeks before enrollment and on the day of randomization.

Key exclusion criteria (21 listed)

Serum potassium ≥6.5 mEq/L within 2 months prior to screening
Unscheduled dialysis for hyperkalemia within the 3 months prior to screening
Hypotension defined as pre-dialysis SBP <100 mm Hg (seated measurement) within 4 weeks prior to enrollment
Recurrent intra-dialytic hypotension, defined as systolic blood pressure <80 mm Hg during ≥3 dialysis sessions per 30-day rolling period or treatment for either hypotension or symptoms of hypotension if systolic blood pressure is < 100 mm Hg during ≥3 dialysis sessions per 30-day rolling period.
Mitral valve repair or replacement

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
Hydralazine/Isorsorbide DinitrateAlso: Apresoline, IsordilHydralazine/Isorsorbide Dinitrate (ISD/HY) will be administered with a target dose of 40 mg of ISD and 75 mg of Hydralazine 3x/daily. Doses will be titrated between weeks 0-4 and may be decreased as necessary for treatment of adverse events. Target Dose: Hydralazine 75 mg 3x day Isorsorbide Dintrate 40 mg 3x/day Allowable Dosage Forms: ISD/HY 10 mg/10-3x/day ISD/HY 20 mg/35 mg-3x/day ISD/HY 40 mg/75 mg-3x/day Dose Titration: ISD/HY will be administered at a starting dose ISD/HY 10 mg/10-3x/day and titrated to ISD/HY 20 mg/35 mg-3x/day after 4 days and to ISD/HY 40 mg/75 mg-3x/day at 4 weeks. Dose will be decreased as necessary for dose-limiting side effects.	Drug	Hydralazine/Isorsorbide Dinitrate
PlaceboPlacebo titration will mimic titration of active study arm	Drug	Placebo

Primary outcome

Rate of Hypotension, Serious Adverse Events, GI Events and Cardiovascular Death
Time frame: 6 months
Rate of primary Safety Outcomes(hypotension, serious adverse events, GI events and CV death)
Efficacy-Change in Coronary Flow Reserve (CFR) From 0-6 Months
Time frame: 0 to 6 months
Primary Efficacy Measure-CFR measured on rest and stress Positron Emission Tomography
Change in E' on TDI Echo From 0-6 Months
Time frame: 0 to 6 months
Co-primary efficacy measure measured on Tissue Doppler Echocardiography
Reduction in Drug Dose or Discontinuation of Study Drug
Time frame: 0 to 6 months
Primary Tolerability measure
Number of Patients Completing Study From 0 to 6 Months
Time frame: 0 to 6 months
Primary Feasibility Measure

2 secondary outcomes

Change in Circulating Fibrosis Markers and Angiogenesis Markers
Time frame: 0 to 6 months
Change in LVMI
Time frame: 0 to 6 months

Results and safety

Results posted to the registry on 27 Apr 2021, as reported by the sponsor. Figures are copied from the record, not re-analysed. Full results on ClinicalTrials.gov.

Participant flow

Group	Started	Completed
Hydralazine/Isorsorbide Dinitrate	7	7
Placebo	10	10

Primary outcome: Rate of Hypotension, Serious Adverse Events, GI Events and Cardiovascular Death

Time frame: 6 months. Count of participants. Unit: Participants

Measure	Hydralazine/Isorsorbide Dinitrate n = 7	Placebo n = 10
intradialytic hpypotension	1	6
SAE	5	3
Nausea	4	3
CV death rate per patient year	0	0

Hydralazine/Isorsorbide Dinitrate vs Placebo: p = 0.04, poisson

Population analysed: intent to treat

Primary outcome: Efficacy-Change in Coronary Flow Reserve (CFR) From 0-6 Months

Time frame: 0 to 6 months. Mean (Standard Deviation). Unit: ratio

Measure	Hydralazine/Isorsorbide Dinitrate n = 6	Placebo n = 10
Value	-0.27 (0.23)	-0.03 (0.46)

Hydralazine/Isorsorbide Dinitrate vs Placebo: p = 0.19, t-test, 2 sided

Population analysed: intent to treat

Primary outcome: Change in E' on TDI Echo From 0-6 Months

Time frame: 0 to 6 months. Mean (Standard Deviation). Unit: cm/s

Measure	Hydralazine/Isorsorbide Dinitrate n = 6	Placebo n = 10
Value	0.56 (1.1)	-0.04 (0.92)

Hydralazine/Isorsorbide Dinitrate vs Placebo: p = 0.34, t-test, 2 sided

Population analysed: intent to treat

Primary outcome: Reduction in Drug Dose or Discontinuation of Study Drug

Time frame: 0 to 6 months. Count of participants. Unit: Participants

Measure	Hydralazine/Isorsorbide Dinitrate n = 7	Placebo n = 10
discontinuation	0	0
reduction	2	3

Population analysed: intent to treat

2 secondary outcomes are reported in the full results.

Adverse events

Time frame: 6 months. Other adverse events reported at 0% frequency or more

Group	Serious adverse events	Other adverse events	Deaths
Hydralazine/Isorsorbide Dinitrate	5 of 7 (71.4%)	7 of 7 (100%)	0 of 7
Placebo	3 of 10 (30%)	10 of 10 (100%)	0 of 10

Limitations and caveats (from the sponsor): small study. unbalanced randomization

Loading the posted results from ClinicalTrials.gov…

Research links

Official record on ClinicalTrials.govLast updated by the sponsor 27 Apr 2021.
Posted resultsParticipant flow, baseline, all outcome measures and adverse events.
Derived from this study: PubMed 33000470Mugendi GA, Mutua FM, Natale P, Esterhuizen TM, Strippoli GF. Calcium channel blockers for people with chronic kidney disease requiring dialysis. Cochrane Database Syst Rev. 2020 Oct 1;10(10):CD011064. doi: 10.1002/14651858.CD011064.pub2.
Individual participant dataSharing planned: Yes. deidentified may be shared upon request to the PI

Related trials for Chronic Hemodialysis (ESRD)

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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.

David Charytan, MD principal investigator

Brigham and Women's Hospital

1 site in 1 country: see every site and its status.

Questions about this trial

What is this clinical trial studying?

A Phase 4 study testing Hydralazine/Isorsorbide Dinitrate in people with Chronic Hemodialysis (ESRD), run by Brigham and Women's Hospital at 1 site 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 21 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 27 Apr 2021. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 1 site 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?

Yes. Results are posted in the registry (first posted 27 Apr 2021). 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?

Rate of Hypotension, Serious Adverse Events, GI Events and Cardiovascular Death (time frame: 6 months). The study lists 5 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 NCT02228408, 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 27 Apr 2021.