Acute Kidney InjuryPhase 2PROTECTNCT02869347
Recombinant Human C1 Esterase Inhibitor in the Prevention of Contrast-induced Nephropathy in High-risk Subjects
A Phase 2 study testing Conestat alfa and Sodium chloride 0.9% in people with Acute Kidney Injury, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
Trial summary
Iodinated contrast media have been causally linked to acute kidney injury known as contrast-induced nephropathy (CIN), which is the consequence of CM-induced local renal ischemia and direct toxic effects. Read more about this study
- Who is it for?
- Ages 18 years and older
- Conditions the study is for
- Acute Kidney Injury
- What is being tested?
- Conestat alfa and Sodium chloride 0.9%
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- Yes, some participants may receive a placebo
- How many people
- 80 participants
- Where
- 1 siteSwitzerland
- Study dates
- Jan 2017to Jul 2018
- 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 years and older
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Estimated glomerular filtration rate (eGFR) of <50 ml/min/1.73m2
- At least one of the following risk factors: diabetes mellitus, age at least 75 years, anemia (baseline hematocrit value less or equal 39% for men and less or equal 36% for women), congestive heart failure class III or IV by New York Heart Association classification, history of pulmonary edema.
Who cannot join
- Contraindications to the class of drugs under study (C1 esterase inhibitors), e.g. known hypersensitivity or allergy to class of drugs or the investigational product
- History of allergy to rabbits
- Current treatment with N-acetylcysteine, sodium bicarbonate, fenoldopam, mannitol (not applicable to mannitol serving as excipient in other medical drugs), dopamine or theophylline
- Women who are pregnant or breast feeding
- Multiple myeloma
- Acute decompensated heart failure (requiring hospital admission and treatment with supplemental oxygen, diuretics and/or vasodilator therapy) within two weeks prior to the date of coronary angiography
Show all 12Show fewer
- Acute myocardial infarction (ST elevation or non-ST elevation myocardial infarction) within two weeks prior to the date of coronary angiography
- Dialysis
- Exposure to iodinated contrast media within seven days prior to the date of coronary angiography.
- Participation in another study with investigational drug within the 30 days preceding and during the present study
- Previous enrolment into the current study
- Enrolment of the investigators and their family members
Trial locations and contacts
1 site in 1 country.
Switzerland1 site
University Hospital Basel
Basel, Canton of Basel-City, 4031
About this study
Official title: Recombinant Human C1 Esterase Inhibitor (Conestat Alfa) in the Prevention of Contrast-induced Nephropathy in High-risk Subjects (PROTECT): a Randomized, Placebo-controlled, Double-blind Single-center Trial
Iodinated contrast media have been causally linked to acute kidney injury known as contrast-induced nephropathy (CIN), which is the consequence of CM-induced local renal ischemia and direct toxic effects. Conestat alfa (recombinant human C1 esterase inhibitor) has been shown to decrease renal ischemic damage in experimental models of renal ischemia.
The Recombinant Human C1 Esterase Inhibitor in the Prevention of Contrast-induced Nephropathy in High-risk Subjects (PROTECT) Study is a randomized, placebo-controlled, double-blind single-center trial that will assess the effect of prophylactic administration of Conestat alfa on the degree of acute kidney injury subjects undergoing elective coronary angiography. Patient with an estimated glomerular filtration rate <=50 ml/min/1.73 m2 and at least one additional risk factor for CIN will be enrolled and randomly assigned to 1) Conestat alfa at 50 U/kg given as intravenous injection immediately before and 4 hours after coronary angiography or 2) placebo (sodium chloride). All patients will receive standard intravenous hydration with isotonic saline. Surrogate markers of kidney injury will be assessed over a 48 hours time period. Patients will be followed for cardiovascular and renal events over 12 weeks.
The primary outcome measure is peak change in urinary Neutrophil gelatinase-associated lipocalin within 48 hours after elective coronary angiography.
Read the detailed description
Iodinated contrast media (CM) are an essential component of contemporary imaging and interventional studies. Although CM are generally well tolerated, they have been causally linked to acute kidney injury known as contrast-induced nephropathy (CIN), the third leading cause of acute kidney injury in hospitalized patients. Preexisting renal impairment, diabetes mellitus, advanced age, congestive heart failure, or large volumes and repeated use of CM have been identified as risk factors for CIN. CIN is the consequence of CM-induced local renal ischemia in combination with direct toxic effects to renal tubular cells. Subsequent inflammation may cause further tissue damage in the reperfusion period. Apart from intravenous hydration preventive strategies for CIN are lacking.
The complement system consists of several circulating proteins that are implicated in the first-line defence against pathogens and in the removal of dying cells. Following renal ischemia activation of the lectin pathway of complement in particular has been associated with local tissue damage in the kidney. Conestat alfa is a recombinant human C1 esterase inhibitor, which inhibits activation of the complement system and is licensed in Europe and USA for the treatment of a hereditary condition (hereditary angioedema). Conestat alfa markedly reduced tissue damage in experimental models of renal ischemia and reperfusion injury, but has not been investigated in human ischemia.
The Recombinant Human C1 Esterase Inhibitor in the Prevention of Contrast-induced Nephropathy in High-risk Subjects (PROTECT) Study is a randomized, placebo-controlled, double-blind single-center trial that will assess the effect of prophylactic administration of Conestat alfa on the degree of acute kidney injury subjects undergoing elective coronary angiography. Patient with an estimated glomerular filtration rate <=50 ml/min/1.73 m2 and at least one additional risk factor for CIN will be enrolled and randomly assigned to 1) Conestat alfa at 50 U/kg given as intravenous injection immediately before and 4 hours after coronary angiography or 2) placebo (sodium chloride). All patients will receive standard intravenous hydration with isotonic saline. Surrogate markers of kidney injury including serum creatinine and cystatin C and urinary Neutrophil gelatinase-associated lipocalin and TIMP2 * Insulin-like growth factor-binding protein 7 (IGFBP7) will be assessed over a 48 hours time period. In addition, increases in troponin T, a marker of cardiac damage, will be assessed. Patients will be followed for thromboembolic, anaphylactic and a composite endpoint of cardiovascular and renal events over a 12 week period.
The primary outcome measure is peak change in urinary Neutrophil gelatinase-associated lipocalin within 48 hours after elective coronary angiography.
Total hydration and contrast media volume will be recorded. Serum C1 esterase inhibitor levels immediately before and 10 minutes after administration of Conestat alfa or placebo will be assessed.
- Conditions
- Acute Kidney Injury
- Being tested
- Conestat alfa, Sodium chloride 0.9%
- Keywords
- recombinant C1 esterase inhibitor, acute kidney injury, coronary angiography, contrast media, Conestat alfa, inflammation
- Medical subject headings
- Acute Kidney Injury, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Conestat alfaDrug
Also called recombinant human C1 esterase inhibitor
Two intravenous injections (over 5 minutes) of Conestat alfa immediately pre-procedure (elective coronary angiography) and 4 hours later; for patients less than 84kg at a dose of 50 U/kg, and for patients of 84kg body weight or greater at a dose of 4200 U.
Sodium chloride 0.9%Drug
Also called isotonic (normal) saline
Two intravenous injections of sodium chloride 0.9% (maximum 28 ml, matching the respective amount of the Conestat alfa arm) immediately pre-procedure (elective coronary angiography) and 4 hours later.
| Study group | Role | What they receive |
|---|---|---|
| Conestat alfa | Active comparator | Intravenous injection of Conestat alfa, for patients less than 84kg at a dose of 50 U/kg, and for patients of 84kg body weight or greater at a dose of 4200 U (2 vials, each diluted in 14ml sterile water). Receives: Drug: Conestat alfa |
| Sodium chloride 0.9% | Placebo comparator | Intravenous injection of sodium chloride 0.9%. Receives: Drug: Sodium chloride 0.9% |
What is being measured
The primary outcome is the main question the study is designed to answer.
Peak change from baseline of urinary Neutrophil gelatinase-associated lipocalin
measured at baseline, 4, 24 and 48 hours
Measured: within 48 hours after contrast exposure
Secondary outcomes (4)
Development of contrast-induced nephropathy
contrast-induced nephropathy is defined as serum creatinine increase of at least 25% or 44micromol/L within 48 hours after coronary angiography
Measured: within 48 hours after contrast exposure
Cystatin C increase of at least 10%
measured at baseline and 24 hours
Measured: within 24 hours after contrast exposure
increase in troponin T
measured at baseline, 4 and 24 hours
Measured: within 24 hours after contrast exposure
Peak change from baseline of urinary TIMP2 * IGFBP7
measured at baseline, 4, 24 and 48 hours
Measured: within 48 hours after contrast exposure
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted16 Aug 2016 (estimated)
- Study startJan 2017
- Primary completionMay 2018
- Study completionJul 2018
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (1)Papers the sponsor has linked to this study.
- Other trials for Acute Kidney InjuryStudies of the same condition, open and under way.
- More trials run by University Hospital, Basel, SwitzerlandThe 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
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 80 participants (actual)
Sponsor and investigators
- Lead sponsor
- University Hospital, Basel, Switzerland
- Sponsor type
- University, hospital or other
- Collaborators
- Pharming Technologies B.V., Clinical Trial Unit, University Hospital Basel, Switzerland
- Responsible party
- Sponsor
- Investigators
- Michael Osthoff, M.D., Principal investigator, University Hospital Basel, Department of Infectious Diseases
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT02869347
- Sponsor's protocol ID
- BASEC 2016-01112
- Acronym
- PROTECT
- Status last verified
- Aug 2018
- First submitted
- 12 Aug 2016
- Last updated
- 8 Aug 2018
- Results posted
- No
- Data monitoring committee
- No
- Individual data sharing
- Undecided
Publications
Panagiotou A, Trendelenburg M, Heijnen IAFM, Moser S, Bonati LH, Breidthardt T, Fahrni G, Kaiser C, Jeger R, Osthoff M. A Randomized Trial of Recombinant Human C1-Esterase-Inhibitor in the Prevention of Contrast-Induced Kidney Injury. JACC Cardiovasc Interv. 2020 Apr 13;13(7):833-842. doi: 10.1016/j.jcin.2019.11.021. Epub 2020 Mar 11.
PubMed 32171721
Study at a glance
From the registry record, last updated by the sponsor on 8 Aug 2018. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Recombinant Human C1 Esterase Inhibitor (Conestat Alfa) in the Prevention of Contrast-induced Nephropathy in High-risk Subjects (PROTECT): a Randomized, Placebo-controlled, Double-blind Single-center Trial
- ClinicalTrials.gov ID
- NCT02869347
- Acronym / sponsor ID
- PROTECT / BASEC 2016-01112
- Conditions
- Acute Kidney Injury
- Keywords
- recombinant C1 esterase inhibitor, acute kidney injury, coronary angiography, contrast media, Conestat alfa, inflammation
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 80 participants (actual)
- Lead sponsor
- University Hospital, Basel, SwitzerlandUniversity, hospital or other
- Collaborators
- Pharming Technologies B.V., Clinical Trial Unit, University Hospital Basel, Switzerland
- Study start
- Jan 2017 (actual)
- Primary completion
- May 2018 (actual)
- Study completion
- Jul 2018 (actual)
- First posted
- 16 Aug 2016 (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.
Iodinated contrast media have been causally linked to acute kidney injury known as contrast-induced nephropathy (CIN), which is the consequence of CM-induced local renal ischemia and direct toxic effects. Conestat alfa (recombinant human C1 esterase inhibitor) has been shown to decrease renal ischemic damage in experimental models of renal ischemia.
The Recombinant Human C1 Esterase Inhibitor in the Prevention of Contrast-induced Nephropathy in High-risk Subjects (PROTECT) Study is a randomized, placebo-controlled, double-blind single-center trial that will assess the effect of prophylactic administration of Conestat alfa on the degree of acute kidney injury subjects undergoing elective coronary angiography. Patient with an estimated glomerular filtration rate <=50 ml/min/1.73 m2 and at least one additional risk factor for CIN will be enrolled and randomly assigned to 1) Conestat alfa at 50 U/kg given as intravenous injection immediately before and 4 hours after coronary angiography or 2) placebo (sodium chloride). All patients will receive standard intravenous hydration with isotonic saline. Surrogate markers of kidney injury will be assessed over a 48 hours time period. Patients will be followed for cardiovascular and renal events over 12 weeks.
The primary outcome measure is peak change in urinary Neutrophil gelatinase-associated lipocalin within 48 hours after elective coronary angiography.
Detailed description
Iodinated contrast media (CM) are an essential component of contemporary imaging and interventional studies. Although CM are generally well tolerated, they have been causally linked to acute kidney injury known as contrast-induced nephropathy (CIN), the third leading cause of acute kidney injury in hospitalized patients. Preexisting renal impairment, diabetes mellitus, advanced age, congestive heart failure, or large volumes and repeated use of CM have been identified as risk factors for CIN. CIN is the consequence of CM-induced local renal ischemia in combination with direct toxic effects to renal tubular cells. Subsequent inflammation may cause further tissue damage in the reperfusion period. Apart from intravenous hydration preventive strategies for CIN are lacking.
The complement system consists of several circulating proteins that are implicated in the first-line defence against pathogens and in the removal of dying cells. Following renal ischemia activation of the lectin pathway of complement in particular has been associated with local tissue damage in the kidney. Conestat alfa is a recombinant human C1 esterase inhibitor, which inhibits activation of the complement system and is licensed in Europe and USA for the treatment of a hereditary condition (hereditary angioedema). Conestat alfa markedly reduced tissue damage in experimental models of renal ischemia and reperfusion injury, but has not been investigated in human ischemia.
The Recombinant Human C1 Esterase Inhibitor in the Prevention of Contrast-induced Nephropathy in High-risk Subjects (PROTECT) Study is a randomized, placebo-controlled, double-blind single-center trial that will assess the effect of prophylactic administration of Conestat alfa on the degree of acute kidney injury subjects undergoing elective coronary angiography. Patient with an estimated glomerular filtration rate <=50 ml/min/1.73 m2 and at least one additional risk factor for CIN will be enrolled and randomly assigned to 1) Conestat alfa at 50 U/kg given as intravenous injection immediately before and 4 hours after coronary angiography or 2) placebo (sodium chloride). All patients will receive standard intravenous hydration with isotonic saline. Surrogate markers of kidney injury including serum creatinine and cystatin C and urinary Neutrophil gelatinase-associated lipocalin and TIMP2 * Insulin-like growth factor-binding protein 7 (IGFBP7) will be assessed over a 48 hours time period. In addition, increases in troponin T, a marker of cardiac damage, will be assessed. Patients will be followed for thromboembolic, anaphylactic and a composite endpoint of cardiovascular and renal events over a 12 week period.
The primary outcome measure is peak change in urinary Neutrophil gelatinase-associated lipocalin within 48 hours after elective coronary angiography.
Total hydration and contrast media volume will be recorded. Serum C1 esterase inhibitor levels immediately before and 10 minutes after administration of Conestat alfa or placebo will be assessed.
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 |
|---|---|---|
| Conestat alfa | Active comparator | Drug: Conestat alfaIntravenous injection of Conestat alfa, for patients less than 84kg at a dose of 50 U/kg, and for patients of 84kg body weight or greater at a dose of 4200 U (2 vials, each diluted in 14ml sterile water). |
| Sodium chloride 0.9% | Placebo comparator | Drug: Sodium chloride 0.9%Intravenous injection of sodium chloride 0.9%. |
Who may qualify
- Ages
- 18 years and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (2 listed)
- Estimated glomerular filtration rate (eGFR) of <50 ml/min/1.73m2
- At least one of the following risk factors: diabetes mellitus, age at least 75 years, anemia (baseline hematocrit value less or equal 39% for men and less or equal 36% for women), congestive heart failure class III or IV by New York Heart Association classification, history of pulmonary edema.
Key exclusion criteria (12 listed)
- Contraindications to the class of drugs under study (C1 esterase inhibitors), e.g. known hypersensitivity or allergy to class of drugs or the investigational product
- History of allergy to rabbits
- Current treatment with N-acetylcysteine, sodium bicarbonate, fenoldopam, mannitol (not applicable to mannitol serving as excipient in other medical drugs), dopamine or theophylline
- Women who are pregnant or breast feeding
- Multiple myeloma
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 |
|---|---|---|
| Conestat alfaAlso: recombinant human C1 esterase inhibitorTwo intravenous injections (over 5 minutes) of Conestat alfa immediately pre-procedure (elective coronary angiography) and 4 hours later; for patients less than 84kg at a dose of 50 U/kg, and for patients of 84kg body weight or greater at a dose of 4200 U. | Drug | Conestat alfa |
| Sodium chloride 0.9%Also: isotonic (normal) salineTwo intravenous injections of sodium chloride 0.9% (maximum 28 ml, matching the respective amount of the Conestat alfa arm) immediately pre-procedure (elective coronary angiography) and 4 hours later. | Drug | Sodium chloride 0.9% |
Primary outcome
Peak change from baseline of urinary Neutrophil gelatinase-associated lipocalin
Time frame: within 48 hours after contrast exposure
measured at baseline, 4, 24 and 48 hours
4 secondary outcomes
Development of contrast-induced nephropathy
Time frame: within 48 hours after contrast exposure
Cystatin C increase of at least 10%
Time frame: within 24 hours after contrast exposure
increase in troponin T
Time frame: within 24 hours after contrast exposure
Peak change from baseline of urinary TIMP2 * IGFBP7
Time frame: within 48 hours after contrast exposure
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 8 Aug 2018.
- Derived from this study: PubMed 32171721Panagiotou A, Trendelenburg M, Heijnen IAFM, Moser S, Bonati LH, Breidthardt T, Fahrni G, Kaiser C, Jeger R, Osthoff M. A Randomized Trial of Recombinant Human C1-Esterase-Inhibitor in the Prevention of Contrast-Induced Kidney Injury. JACC Cardiovasc Interv. 2020 Apr 13;13(7):833-842. doi: 10.1016/j.jcin.2019.11.021. Epub 2020 Mar 11.
- Individual participant dataSharing planned: Undecided
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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.
Michael Osthoff, M.D. principal investigator
University Hospital Basel, Department of Infectious Diseases
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 Conestat alfa and Sodium chloride 0.9% in people with Acute Kidney Injury, run by University Hospital, Basel, Switzerland at 1 site in Switzerland.
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 12 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 8 Aug 2018. 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 Switzerland. 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?
Peak change from baseline of urinary Neutrophil gelatinase-associated lipocalin (time frame: within 48 hours after contrast exposure). 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 NCT02869347, 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 8 Aug 2018.