Chronic Kidney DiseasePhase 2NCT00817037
Sitaxsentan in Proteinuric Chronic Kidney Disease
A Phase 2 study testing Sitaxsentan and Nifedipine in people with Chronic Kidney Disease and Proteinuria, run by University of Edinburgh at 1 site in United Kingdom.
Trial summary
Patients with chronic kidney disease (CKD) have higher blood pressures than the general population. They also tend to have protein leaking into the urine (proteinuria). CKD, high blood pressure and proteinuria independently and together increase the risk of developing atherosclerosis (hardening) of the arteries that… Read more about this study
- Who is it for?
- Ages 18 to 70 years
- Conditions the study is for
- Chronic Kidney Disease, Proteinuria, Blood Pressure
- What is being tested?
- Sitaxsentan and Nifedipine
- Type of treatment
- Pill or oral medicine
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 27 participants
- Where
- 1 siteUnited Kingdom
- Study dates
- 14 Jul 2007to 7 Jul 2009
- Phase
- Phase 2
- 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 70 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Has Stage 1-5 chronic kidney disease (CKD) as defined by the Kidney Disease Outcomes Quality Initiative (using the Cockcroft and Gault equation for calculation of glomerular filtration rate) with proteinuria, including any of the following aetiologies: immunoglobulin A (IgA) nephropathy, polycystic kidney disease (PCKD), congenital abnormalities, reflux nephropathy, focal segmental glomerulosclerosis, minimal change nephropathy, and membranous nephropathy.
- Is between 18 and 70 years of age, inclusive.
- Has a body mass index (BMI) between 18 and 35 kg/m2, inclusive.
- Is willing and able to adhere to the protocol requirements.
- Provides written informed consent before any study procedure is performed.
Who cannot join
- Requires peritoneal dialysis or haemodialysis.
- Has kidney disease due to diabetes mellitus, vasculitis, systemic lupus erythematosus, or known renovascular disease; antiglomerular basement membrane disease; or is on immunosuppressive medication.
- Has a serum albumin in the nephrotic range (< 30 g/L) during Screening.
- Has a sustained sitting systolic blood pressure (BP) > 160 mmHg or sustained sitting diastolic BP > 100 mmHg during Screening.
- Has postural hypotension during Screening, which is defined as a decrease in systolic BP ≥ 20 mmHg and/or a decrease in diastolic BP ≥ 10 mmHg, comparing sitting and standing measurements.
- Has a history and/or evidence of ischaemic heart disease.
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- Has or had a malignancy, with the exception of adequately-treated basal cell or squamous cell carcinoma of the skin, that required significant medical intervention within the past 3 months and/or is likely to result in death within the next 2 years.
- Has a history of allergies or hypersensitivity to sitaxsentan or nifedipine or the excipients of either drug.
- Has a clinically significant psychiatric, addictive, neurological disease or any other condition that, in the Investigator's opinion, would compromise his/her ability to give informed consent, participate fully in this study, prevent adherence to the requirements of the study protocol, or would compromise the interpretation of the data obtained from this study.
- Uses a prohibited medication or plans to use a prohibited medication during the study.
- Prohibited medications include cyclosporine A, alternative endothelin (ET) receptor antagonists, phosphodiesterase inhibitors, and/or vitamin K antagonists (e.g., warfarin). The intermittent use of phosphodiesterase inhibitors (e.g., sildenafil) "as needed" for erectile dysfunction is acceptable, however, as long as the subject is not dosed within 24 hours of an efficacy assessment.
- Received treatment with an investigational drug or device within 30 days prior to study entry.
- Has a history of organ transplantation.
- Has atrial fibrillation requiring anticoagulation or a history (in the preceding 6 months) of any intermittent cardiac dysrhythmia that may require anticoagulation therapy.
- Has an alanine aminotransferase (ALT) and/or aspartate aminotransferase (AST) level > 1.5 × the upper limit of the normal range (ULN) at Screening and/or serum total bilirubin > ULN.
- Has a haemoglobin concentration < 8.0 mg/dL at Screening.
- Has positive serological results for hepatitis B and/or hepatitis C.
- Is a woman of childbearing potential who is unwilling to use 2 forms of contraceptive therapy, including at least 1 barrier method, throughout the study. (Women who are surgically sterile or who are post-menopausal for at least 2 years are not considered to be of childbearing potential.)
- Is pregnant, lactating, or breastfeeding.
- Has, in the opinion of the Investigator, a dependence on alcohol.
- Has, in the opinion of the Investigator, a dependence on illicit drugs.
Trial locations and contacts
1 site in 1 country.
United Kingdom1 site
Clinical Research Centre, Western General Hospital
Edinburgh, Scotland, EH4 2XU
About this study
Official title: The Effect of Sitaxsentan Once Daily Dosing on Proteinuria, 24-hour Systemic Blood Pressure, and Arterial Stiffness in Subjects With Chronic Kidney Disease
Patients with chronic kidney disease (CKD) have higher blood pressures than the general population. They also tend to have protein leaking into the urine (proteinuria). CKD, high blood pressure and proteinuria independently and together increase the risk of developing atherosclerosis (hardening) of the arteries that leads to diseases such as heart attack and stroke. Although there are a number of drugs available that lower blood pressure, these are not always fully effective. Furthermore, there are even fewer drugs that simultaneously lower blood pressure, reduce proteinuria, and slow down kidney damage in CKD.
Recent research has shown that drugs like sitaxsentan not only lower blood pressure but also reduce proteinuria and potentially slow down the progression of CKD [1,2]. Before sitaxsentan can become freely available to individuals with CKD it is important to look at the effects this drug could have on proteinuria and blood pressure.
- Goddard J, Johnston NR, Hand MF, et al. Endothelin-A receptor antagonism reduces blood pressure and increases renal blood flow in hypertensive patients with chronic renal failure: a comparison of selective and combined endothelin receptor blockade. Circulation 2004;109:1186-1193.
- Krum H, Viskoper RJ, Lacourciere Y et al. The effect of an endothelin receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. New Engl J Med 1998;338:784-790.
- Conditions
- Chronic Kidney Disease, Proteinuria, Blood Pressure
- Being tested
- Sitaxsentan, Nifedipine, Placebo tablet
- Keywords
- Chronic kidney disease, Proteinuria, Blood pressure, Arterial stiffness, Endothelin antagonist, Sitaxsentan
- Medical subject headings
- Renal Insufficiency, Chronic, Proteinuria
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
SitaxsentanDrug
Also called Thelin
Sitaxsentan 100mg once daily oral dosing for 6 weeks
NifedipineDrug
Also called Adalat LA
Nifedipine 30mg once daily oral dosing for 6 weeks
Placebo tabletDrug
Placebo tablet once daily oral dosing for 6 weeks
| Study group | Role | What they receive |
|---|---|---|
| Sitaxsentan | Experimental | Once daily oral sitaxsentan 100mg given over a period of 6 weeks.
24hr proteinuria, 24hr blood pressure and arterial stiffness measured at day 1, week 3 and week 6 of treatment Receives: Drug: Sitaxsentan |
| Placebo | Placebo comparator | Once daily oral placebo tablet given over a period of 6 weeks.
24hr proteinuria, 24hr blood pressure and arterial stiffness measured at day 1, week 3 and week 6 of treatment Receives: Drug: Placebo tablet |
| Nifedipine | Active comparator | Open labeled active comparator
Once daily oral nifedipine 30mg given over a period of 6 weeks.
24hr proteinuria, 24hr blood pressure and arterial stiffness measured at day 1, week 3 and week 6 of treatment Receives: Drug: Nifedipine |
What is being measured
The primary outcome is the main question the study is designed to answer.
The principal objective of this study is to evaluate whether sitaxsentan reduces proteinuria in people with chronic kidney disease.
Measured: 6 Weeks
Secondary outcomes (3)
Secondary objective of this study is to evaluate whether sitaxsentan reduces systemic blood pressure in people with chronic kidney disease.
Measured: 6 weeks
Secondary objective is to determine whether sitaxsentan improves indices of arterial stiffness in people with chronic kidney disease
Measured: 6 weeks
Secondary objectives is to determine the safety of sitaxsentan in chronic kidney disease
Measured: 6 weeks
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted6 Jan 2009 (estimated)
- Study start14 Jul 2007
- Primary completion7 Jul 2009
- Study completion7 Jul 2009
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Chronic Kidney DiseaseStudies of the same condition, open and under way.
- More trials run by University of EdinburghThe 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 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind
- Who is masked
- Participant, Care provider, Investigator
- Enrolment
- 27 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Edinburgh
- Sponsor type
- University, hospital or other
- Collaborators
- Encysive Pharmaceuticals
- Responsible party
- Sponsor
- Investigators
- David Webb, MD DSc FRCP FRSE FMedSci, Study director, University of EdinburghNeeraj Dhaun, MBChB, Principal investigator, University of Edinburgh
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00817037
- Sponsor's protocol ID
- 2007/W/CRC/02
- Other IDs
- CTA# 2006-002004-33, 06/MRE10/69
- Status last verified
- Feb 2025
- First submitted
- 5 Jan 2009
- Last updated
- 7 Feb 2025
- Results posted
- No
- Data monitoring committee
- Yes
Study at a glance
From the registry record, last updated by the sponsor on 7 Feb 2025. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- The Effect of Sitaxsentan Once Daily Dosing on Proteinuria, 24-hour Systemic Blood Pressure, and Arterial Stiffness in Subjects With Chronic Kidney Disease
- ClinicalTrials.gov ID
- NCT00817037
- Acronym / sponsor ID
- 2007/W/CRC/02
- Conditions
- Chronic Kidney Disease, Proteinuria, Blood Pressure
- Keywords
- Chronic kidney disease, Proteinuria, Blood pressure, Arterial stiffness, Endothelin antagonist, Sitaxsentan
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 27 participants (actual)
- Lead sponsor
- University of EdinburghUniversity, hospital or other
- Collaborators
- Encysive Pharmaceuticals
- Study start
- 14 Jul 2007 (actual)
- Primary completion
- 7 Jul 2009 (actual)
- Study completion
- 7 Jul 2009 (actual)
- First posted
- 6 Jan 2009 (estimated)
- 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.
Patients with chronic kidney disease (CKD) have higher blood pressures than the general population. They also tend to have protein leaking into the urine (proteinuria). CKD, high blood pressure and proteinuria independently and together increase the risk of developing atherosclerosis (hardening) of the arteries that leads to diseases such as heart attack and stroke. Although there are a number of drugs available that lower blood pressure, these are not always fully effective. Furthermore, there are even fewer drugs that simultaneously lower blood pressure, reduce proteinuria, and slow down kidney damage in CKD.
Recent research has shown that drugs like sitaxsentan not only lower blood pressure but also reduce proteinuria and potentially slow down the progression of CKD [1,2]. Before sitaxsentan can become freely available to individuals with CKD it is important to look at the effects this drug could have on proteinuria and blood pressure.
- Goddard J, Johnston NR, Hand MF, et al. Endothelin-A receptor antagonism reduces blood pressure and increases renal blood flow in hypertensive patients with chronic renal failure: a comparison of selective and combined endothelin receptor blockade. Circulation 2004;109:1186-1193.
- Krum H, Viskoper RJ, Lacourciere Y et al. The effect of an endothelin receptor antagonist, bosentan, on blood pressure in patients with essential hypertension. New Engl J Med 1998;338:784-790.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Triple blind (participant, care provider, investigator)
- Number of arms
- 3
| Arm | Type | Receives |
|---|---|---|
| Sitaxsentan | Experimental | Drug: SitaxsentanOnce daily oral sitaxsentan 100mg given over a period of 6 weeks. 24hr proteinuria, 24hr blood pressure and arterial stiffness measured at day 1, week 3 and week 6 of treatment |
| Placebo | Placebo comparator | Drug: Placebo tabletOnce daily oral placebo tablet given over a period of 6 weeks. 24hr proteinuria, 24hr blood pressure and arterial stiffness measured at day 1, week 3 and week 6 of treatment |
| Nifedipine | Active comparator | Drug: NifedipineOpen labeled active comparator Once daily oral nifedipine 30mg given over a period of 6 weeks. 24hr proteinuria, 24hr blood pressure and arterial stiffness measured at day 1, week 3 and week 6 of treatment |
Who may qualify
- Ages
- 18 to 70 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (5 listed)
- Has Stage 1-5 chronic kidney disease (CKD) as defined by the Kidney Disease Outcomes Quality Initiative (using the Cockcroft and Gault equation for calculation of glomerular filtration rate) with proteinuria, including any of the following aetiologies: immunoglobulin A (IgA) nephropathy, polycystic kidney disease (PCKD), congenital abnormalities, reflux nephropathy, focal segmental glomerulosclerosis, minimal change nephropathy, and membranous nephropathy.
- Is between 18 and 70 years of age, inclusive.
- Has a body mass index (BMI) between 18 and 35 kg/m2, inclusive.
- Is willing and able to adhere to the protocol requirements.
- Provides written informed consent before any study procedure is performed.
Key exclusion criteria (21 listed)
- Requires peritoneal dialysis or haemodialysis.
- Has kidney disease due to diabetes mellitus, vasculitis, systemic lupus erythematosus, or known renovascular disease; antiglomerular basement membrane disease; or is on immunosuppressive medication.
- Has a serum albumin in the nephrotic range (< 30 g/L) during Screening.
- Has a sustained sitting systolic blood pressure (BP) > 160 mmHg or sustained sitting diastolic BP > 100 mmHg during Screening.
- Has postural hypotension during Screening, which is defined as a decrease in systolic BP ≥ 20 mmHg and/or a decrease in diastolic BP ≥ 10 mmHg, comparing sitting and standing measurements.
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 |
|---|---|---|
| SitaxsentanAlso: ThelinSitaxsentan 100mg once daily oral dosing for 6 weeks | Drug | Sitaxsentan |
| NifedipineAlso: Adalat LANifedipine 30mg once daily oral dosing for 6 weeks | Drug | Nifedipine |
| Placebo tabletPlacebo tablet once daily oral dosing for 6 weeks | Drug | Placebo |
Primary outcome
The principal objective of this study is to evaluate whether sitaxsentan reduces proteinuria in people with chronic kidney disease.
Time frame: 6 Weeks
3 secondary outcomes
Secondary objective of this study is to evaluate whether sitaxsentan reduces systemic blood pressure in people with chronic kidney disease.
Time frame: 6 weeks
Secondary objective is to determine whether sitaxsentan improves indices of arterial stiffness in people with chronic kidney disease
Time frame: 6 weeks
Secondary objectives is to determine the safety of sitaxsentan in chronic kidney disease
Time frame: 6 weeks
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 7 Feb 2025.
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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 Webb, MD DSc FRCP FRSE FMedSci study director
University of Edinburgh
Neeraj Dhaun, MBChB principal investigator
University of Edinburgh
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Sitaxsentan and Nifedipine in people with Chronic Kidney Disease and Proteinuria, run by University of Edinburgh at 1 site in United Kingdom.
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 7 Feb 2025. 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 Kingdom. 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 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
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 is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
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?
The principal objective of this study is to evaluate whether sitaxsentan reduces proteinuria in people with chronic kidney disease. (time frame: 6 Weeks). 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 7 Feb 2025.