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

NCT02869347 | Completed Phase 2

• 1 other identifier: BASEC 2016-01112
• Study Type: interventional
• Target: 80
• Locations: 1 country
• Sites: 1

Brief 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.

Conditions

Acute Kidney Injury

Keywords

recombinant C1 esterase inhibitor; acute kidney injury; coronary angiography; contrast media; Conestat alfa; inflammation

Outcome Measures

Primary Outcomes (1)

• Peak change from baseline of urinary Neutrophil gelatinase-associated lipocalin

  measured at baseline, 4, 24 and 48 hours

  within 48 hours after contrast exposure

Secondary Outcomes (4)

• Development of contrast-induced nephropathy

  within 48 hours after contrast exposure

• Cystatin C increase of at least 10%

  within 24 hours after contrast exposure

• increase in troponin T

  within 24 hours after contrast exposure

• Peak change from baseline of urinary TIMP2 * IGFBP7

  within 48 hours after contrast exposure

Other Outcomes (4)

• Composite cardiovascular and renal outcome

  within 12-weeks after first intervention

• Thromboembolic events

  within 12-weeks after first intervention

• Anaphylactic reaction

  within 24 hours after first intervention

Study Arms (2)

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).

Drug: Conestat alfa

Sodium chloride 0.9%

PLACEBO COMPARATOR

Intravenous injection of sodium chloride 0.9%.

Drug: Sodium chloride 0.9%

Interventions

Conestat alfa DRUG

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.

Also known as: recombinant human C1 esterase inhibitor

Conestat alfa

Sodium chloride 0.9% DRUG

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.

Also known as: isotonic (normal) saline

Sodium chloride 0.9%

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

• 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.

You may not qualify if:

• 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

Sponsors & Collaborators

• University Hospital, Basel, Switzerland: lead
• Pharming Technologies B.V.: collaborator
• Clinical Trial Unit, University Hospital Basel, Switzerland: collaborator

Study Sites (1)

University Hospital Basel

Basel, Canton of Basel-City, 4031, Switzerland

Location

Related Publications (1)

• 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.

  PMID: 32171721 DERIVED

MeSH Terms

Conditions

Acute Kidney Injury; Inflammation

Interventions

conestat alfa; Sodium Chloride

Condition Hierarchy (Ancestors)

Renal Insufficiency; Kidney Diseases; Urologic Diseases; Female Urogenital Diseases; Female Urogenital Diseases and Pregnancy Complications; Urogenital Diseases; Male Urogenital Diseases; Pathologic Processes; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Chlorides; Hydrochloric Acid; Chlorine Compounds; Inorganic Chemicals; Sodium Compounds

Study Officials

• Michael Osthoff, M.D.

  University Hospital Basel, Department of Infectious Diseases

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: QUADRUPLE
• Who Masked: PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: PREVENTION
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: August 12, 2016
• First Posted: August 16, 2016
• Study Start: January 1, 2017
• Primary Completion: May 1, 2018
• Study Completion: July 1, 2018
• Last Updated: August 8, 2018

Record last verified: 2018-08

Locations

CH (1)