Recombinant Human C1 Esterase Inhibitor in the Prevention of Contrast-induced Nephropathy in High-risk Subjects

• Status: Completed
• Trial end date: 2018-07-01
• Target enrollment: 0
• Participant gender: All

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. 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.

• Phase: Phase 2
• Accepts Healthy Volunteers?: No

Details

• Lead Sponsor: University Hospital, Basel, Switzerland
• Collaborators: Clinical Trial Unit, University Hospital Basel, Switzerland; Pharming Technologies B.V.
• Treatments: Complement C1 Inactivator Proteins; Complement C1 Inhibitor Protein; Complement C1s

Criteria

Inclusion Criteria:

• 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.

Exclusion Criteria:

• 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

• 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