Contrast Induced NephropathyPhase 1CIN-NACNCT00575419
Safety Study Of N-Acetylcysteine For Prevention Of Contrast Induced Nephropathy In Patients w/Stage 3 Renal Failure
A Phase 1 study testing N-acetylcysteine in people with Contrast Induced Nephropathy, run by Oregon Health and Science University at 1 site in United States.
Trial summary
This will be a randomized prospective dose escalation clinical study of N-acetylcysteine (NAC) in patients with stage 3 or worse renal failure (Glomerular Filtration Rate 30-60 ml/min calculated with the Modification of Diet in Renal Disease formula), undergoing a procedure or imaging that requires the administration… Read more about this study
- Who is it for?
- Ages 18 to 85 years
- Conditions the study is for
- Contrast Induced Nephropathy
- What is being tested?
- N-acetylcysteine
- Type of treatment
- Injection or infusion
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 6 participants
- Where
- 1 siteUnited States
- Study dates
- Nov 2007to 15 Sep 2014
- Phase
- Phase 1
- 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 85 years
- All sexes
- No healthy volunteers
- Adult, Older adult
Who may be able to join
- Renal failure, stage 3 or worse
- Undergoing endovascular procedure with an isotonic, non ionized contrast agent
- Life expectancy at least 4 weeks from date of registration
- Platelets greater than or equal to 100,000/mm3
- Systolic pressure of greater than 90 mm Hg
- No contraindications to N-Ac or contrast agent
- Not at risk for general anesthesia
Who cannot join
- Acute renal failure
- Undergoing dialysis
- Decompensate cardiac failure
- Pregnant or nursing
- History of clinically significant reactive airway disease
- Receiving non-steroidal anti-inflammatory agent within 24 hours of study
Trial locations and contacts
1 site in 1 country.
United States1 site
Oregon Health & Science University
Portland, Oregon, 97239
About this study
Official title: Dose Escalation Study Of I.V. And Intra-Aortic N-Acetylcysteine For The Prevention Of Contrast Induced Nephropathy In Patients With Stage 3 Renal Failure Undergoing Contrast Imaging Studies: A Phase I Trial
This will be a randomized prospective dose escalation clinical study of N-acetylcysteine (NAC) in patients with stage 3 or worse renal failure (Glomerular Filtration Rate 30-60 ml/min calculated with the Modification of Diet in Renal Disease formula), undergoing a procedure or imaging that requires the administration of contrast media at Oregon Health \& Science University or the Portland Veterans Hospital. Subjects will receive NAC 60 minutes prior to the procedure or imaging requiring contrast media. Toxicity will be graded according to NCI Common Toxicity Criteria (CTC) version 3.0. An adult Phase 1 dose escalation study of NAC administered intravenously (IV) and intra-arterially (IA) will be performed. An isotonic nonionic contrast agent will be used in all cases. Contrast Induced Nephropathy (CIN) is defined as an increase in serum creatinine concentration of 25% or more from the subjects baseline value within a 72-hour period after the administration of contrast media. Serum creatinine concentration will be measured at admission, every day during in-patient hospitalization, and at hospital discharge.
Read the detailed description
Radiographic contrast media is being used at an increasing rate for various diagnostic and therapeutic procedures. Renal failure following contrast administration for enhanced imaging has become a serious complication. Patients with underlying renal disorders have an increased incidence of Contrast Induced Nephropathy (CIN). CIN has been reported as the third most common cause of in-hospital renal failure after hypovolemia and post surgical renal insufficiency. Several factors increase the risk of CIN: preexisting renal dysfunction, volume and type of contrast agent employed, and lack of renal prophylaxis. CIN pathogenesis may be due to an injury to the renal cortex and outer medulla resulting from a decrease in blood flow, an osmotic effect, and/or direct toxicity to tubular cells by oxygen free radicals. N-acetylcysteine (NAC) is a cysteine analog and sulfur-containing agent, with strong antioxidant activity, which induces de novo synthesis of glutathione. NAC protection during the evolution of renal failure may be related to the ability to scavenge oxygen free radicals and/or improve endothelium-dependant vasodilation. There is no animal model that directly correlates with CIN, but the investigators have investigated nephrotoxicity and chemoprotection against cisplatin induced nephropathy which has a mechanism of action mediated through the generation of reactive intermediates in an animal model. NAC is potentially protective against cisplatin induced nephrotoxicity when administered at high intravenous (IV) doses (400 mg/kg) and at low intra-arterial (IA) doses (50mg/kg) down the descending aorta. This implies a safe dose-dependent effect of IV NAC and that lower doses can be used IA safely.
Objectives:
Primary Objective:
The primary objective of this study is to establish a maximum tolerated dose of both IV and IA NAC. This maximum tolerated dose will be evaluated primarily for efficacy in a future study.
Secondary Objectives:
- To obtain data on changes from baseline serum creatinine and calculated creatinine clearance to provide sample size estimates for future studies.
- To estimate the efficacy of NAC in reducing the incidence of CIN. While this study is not adequately powered to address this objective, analyses will be run to assess an increase in serum creatinine concentration of 25% or more from the baseline value within a 48-72 hour period after a procedure or imaging that requires the administration of contrast media as a surrogate for CIN incidence.
- To determine NAC pharmacology administered IV or IA.
- Conditions
- Contrast Induced Nephropathy
- Being tested
- N-acetylcysteine
- Keywords
- Contrast Induced Nephropathy
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
N-acetylcysteineDrug
- Dose Level 1: 150 mg/kg/day
- Dose Level 2: 300 mg/kg/day
- Dose Level 3: 600 mg/kg/day
- Dose Level 4: 900 mg/kg/day
- Dose Level 5: 1200 mg/kg/day
| Study group | Role | What they receive |
|---|---|---|
| 1, IV NAC | Experimental | N-acetylcysteine administered intravenously Receives: Drug: N-acetylcysteine |
| 2, IA NAC | Experimental | N-acetylcysteine administered intra-arterial Receives: Drug: N-acetylcysteine |
What is being measured
The primary outcome is the main question the study is designed to answer.
Toxicity will be graded according to NCI CTCAE version 3.0.
Measured: 2 years
Secondary outcomes (3)
Baseline serum creatinine and calculated creatinine clearance to provide sample size estimates for future studies.
Measured: 2 years
To estimate the efficacy of NAC in reducing the incidence of CIN.
Measured: 2 years
To determine NAC pharmacology administered IV or IA.
Measured: 2 years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted18 Dec 2007 (estimated)
- Study startNov 2007
- Primary completion15 Sep 2014
- Study completion15 Sep 2014
Why it stopped: Low accrual
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 Contrast Induced NephropathyStudies of the same condition, open and under way.
- More trials run by Oregon Health and Science UniversityThe 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 1
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind
- Who is masked
- Participant
- Enrolment
- 6 participants (actual)
Sponsor and investigators
- Lead sponsor
- Oregon Health and Science University
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Edward Neuwelt, Oregon Health and Science University
- Investigators
- Edward A Neuwelt, MD, Principal investigator, Oregon Health and Science University
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT00575419
- Sponsor's protocol ID
- OHSU-3673
- Acronym
- CIN-NAC
- Status last verified
- Jul 2019
- First submitted
- 14 Dec 2007
- Last updated
- 2 Aug 2019
- Results posted
- No
- Data monitoring committee
- Yes
Publications
Stenstrom DA, Muldoon LL, Armijo-Medina H, Watnick S, Doolittle ND, Kaufman JA, Peterson DR, Bubalo J, Neuwelt EA. N-acetylcysteine use to prevent contrast medium-induced nephropathy: premature phase III trials. J Vasc Interv Radiol. 2008 Mar;19(3):309-18. doi: 10.1016/j.jvir.2007.11.003.
PubMed 18295688
Study at a glance
From the registry record, last updated by the sponsor on 2 Aug 2019. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Dose Escalation Study Of I.V. And Intra-Aortic N-Acetylcysteine For The Prevention Of Contrast Induced Nephropathy In Patients With Stage 3 Renal Failure Undergoing Contrast Imaging Studies: A Phase I Trial
- ClinicalTrials.gov ID
- NCT00575419
- Acronym / sponsor ID
- CIN-NAC / OHSU-3673
- Conditions
- Contrast Induced Nephropathy
- Keywords
- Contrast Induced Nephropathy
- Phase
- Phase 1
- Study type
- Interventional
- Recruitment status
- TerminatedReason stopped: Low accrual
- Enrolment
- 6 participants (actual)
- Lead sponsor
- Oregon Health and Science UniversityUniversity, hospital or other
- Study start
- Nov 2007 (actual)
- Primary completion
- 15 Sep 2014 (actual)
- Study completion
- 15 Sep 2014 (actual)
- First posted
- 18 Dec 2007 (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.
This will be a randomized prospective dose escalation clinical study of N-acetylcysteine (NAC) in patients with stage 3 or worse renal failure (Glomerular Filtration Rate 30-60 ml/min calculated with the Modification of Diet in Renal Disease formula), undergoing a procedure or imaging that requires the administration of contrast media at Oregon Health \& Science University or the Portland Veterans Hospital. Subjects will receive NAC 60 minutes prior to the procedure or imaging requiring contrast media. Toxicity will be graded according to NCI Common Toxicity Criteria (CTC) version 3.0. An adult Phase 1 dose escalation study of NAC administered intravenously (IV) and intra-arterially (IA) will be performed. An isotonic nonionic contrast agent will be used in all cases. Contrast Induced Nephropathy (CIN) is defined as an increase in serum creatinine concentration of 25% or more from the subjects baseline value within a 72-hour period after the administration of contrast media. Serum creatinine concentration will be measured at admission, every day during in-patient hospitalization, and at hospital discharge.
Detailed description
Radiographic contrast media is being used at an increasing rate for various diagnostic and therapeutic procedures. Renal failure following contrast administration for enhanced imaging has become a serious complication. Patients with underlying renal disorders have an increased incidence of Contrast Induced Nephropathy (CIN). CIN has been reported as the third most common cause of in-hospital renal failure after hypovolemia and post surgical renal insufficiency. Several factors increase the risk of CIN: preexisting renal dysfunction, volume and type of contrast agent employed, and lack of renal prophylaxis. CIN pathogenesis may be due to an injury to the renal cortex and outer medulla resulting from a decrease in blood flow, an osmotic effect, and/or direct toxicity to tubular cells by oxygen free radicals. N-acetylcysteine (NAC) is a cysteine analog and sulfur-containing agent, with strong antioxidant activity, which induces de novo synthesis of glutathione. NAC protection during the evolution of renal failure may be related to the ability to scavenge oxygen free radicals and/or improve endothelium-dependant vasodilation. There is no animal model that directly correlates with CIN, but the investigators have investigated nephrotoxicity and chemoprotection against cisplatin induced nephropathy which has a mechanism of action mediated through the generation of reactive intermediates in an animal model. NAC is potentially protective against cisplatin induced nephrotoxicity when administered at high intravenous (IV) doses (400 mg/kg) and at low intra-arterial (IA) doses (50mg/kg) down the descending aorta. This implies a safe dose-dependent effect of IV NAC and that lower doses can be used IA safely.
Objectives:
Primary Objective:
The primary objective of this study is to establish a maximum tolerated dose of both IV and IA NAC. This maximum tolerated dose will be evaluated primarily for efficacy in a future study.
Secondary Objectives:
- To obtain data on changes from baseline serum creatinine and calculated creatinine clearance to provide sample size estimates for future studies.
- To estimate the efficacy of NAC in reducing the incidence of CIN. While this study is not adequately powered to address this objective, analyses will be run to assess an increase in serum creatinine concentration of 25% or more from the baseline value within a 48-72 hour period after a procedure or imaging that requires the administration of contrast media as a surrogate for CIN incidence.
- To determine NAC pharmacology administered IV or IA.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- Single blind (participant)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| 1, IV NAC | Experimental | Drug: N-acetylcysteineN-acetylcysteine administered intravenously |
| 2, IA NAC | Experimental | Drug: N-acetylcysteineN-acetylcysteine administered intra-arterial |
Who may qualify
- Ages
- 18 to 85 years
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Adult, Older adult
Key inclusion criteria (7 listed)
- Renal failure, stage 3 or worse
- Undergoing endovascular procedure with an isotonic, non ionized contrast agent
- Life expectancy at least 4 weeks from date of registration
- Platelets greater than or equal to 100,000/mm3
- Systolic pressure of greater than 90 mm Hg
Key exclusion criteria (6 listed)
- Acute renal failure
- Undergoing dialysis
- Decompensate cardiac failure
- Pregnant or nursing
- History of clinically significant reactive airway disease
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 |
|---|---|---|
| N-acetylcysteine* Dose Level 1: 150 mg/kg/day * Dose Level 2: 300 mg/kg/day * Dose Level 3: 600 mg/kg/day * Dose Level 4: 900 mg/kg/day * Dose Level 5: 1200 mg/kg/day | Drug | 1, IV NAC, 2, IA NAC |
Primary outcome
Toxicity will be graded according to NCI CTCAE version 3.0.
Time frame: 2 years
3 secondary outcomes
Baseline serum creatinine and calculated creatinine clearance to provide sample size estimates for future studies.
Time frame: 2 years
To estimate the efficacy of NAC in reducing the incidence of CIN.
Time frame: 2 years
To determine NAC pharmacology administered IV or IA.
Time frame: 2 years
Results and safety
The study was stopped early (reason given: Low accrual). Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Aug 2019.
- Results publication: PubMed 18295688Stenstrom DA, Muldoon LL, Armijo-Medina H, Watnick S, Doolittle ND, Kaufman JA, Peterson DR, Bubalo J, Neuwelt EA. N-acetylcysteine use to prevent contrast medium-induced nephropathy: premature phase III trials. J Vasc Interv Radiol. 2008 Mar;19(3):309-18. doi: 10.1016/j.jvir.2007.11.003.
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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.
Edward A Neuwelt, MD principal investigator
Oregon Health and Science University
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 1 study testing N-acetylcysteine in people with Contrast Induced Nephropathy, run by Oregon Health and Science University 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 7 inclusion and 6 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: stopped early, as of the sponsor's last update on 2 Aug 2019. 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 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.
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 was stopped early (reason given: Low accrual). Results are not available in the source record.
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?
Toxicity will be graded according to NCI CTCAE version 3.0. (time frame: 2 years). 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 NCT00575419, 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 2 Aug 2019.