Acute Kidney InjuryACCENTNCT04442516
Cisplatin Induced Kidney Toxicity
An observational study of Acute Kidney Injury and Cancer, run by The Hospital for Sick Children at 1 site in Canada.
Trial summary
Cisplatin (CisP) is a chemotherapeutic agent used to treat head and neck and lung cancer in adults and over 15 different pediatric cancers. Despite its known toxicity, CisP is still widely used as a first line chemotherapy as it is so effective. Read more about this study
- Who is it for?
- Ages 3 months and older
- Conditions the study is for
- Acute Kidney Injury, Cancer
- What is being tested?
- Questionnaire, sampling of blood, urine and saliva
- How many people
- 600 participants
- Where
- 1 siteCanada
- Study dates
- 12 Aug 2020to 31 Dec 2028
- Phase
- Observational
- Are there results?
- Not yet: the study is under way
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 3 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Study population: Child Cohort. We already performed these study procedures on 159 children in the "ABLE" study, a 12-centre cohort study.Eligibility criteria and data/samples collected on these patients during their initial CisP treatment are almost identical to the present study. The cohort diagnoses include neuroblastoma, medulloblastoma, osteosarcoma, germ cell tumour, hepatoblastoma, and other cancers. Data and specimens from the pediatric study subjects in the ABLE study who were recruited during their first CisP infusion (about half) will be included in the current study. The remaining children (to reach a target of 300) will be recruited over 3 years from the following centres: McGill, UBC, SickKids, U. Manitoba and UWO. Adult Cohort. 300 adults (18 years of age or older) initiating CisP (≥75 mg/m2) treatment for head/neck or lung cancers will be recruited to participate in this study from PMH (Toronto), UBC and UWO over 2 years. Over 500 new patients/year are available across all sites.
Who may be able to join
- Adult participants: Initiating treatment with CisP (≥75 mg/m2) for head/neck or lung cancers at one of the Adult participating sites; 18 years of age or older.
- Paediatric participants: Initiating treatment with CisP for any cancer diagnosis at one of the Pediatric participating sites; greater than 3 months of age.
- All participants: Consent to participate in the study.
Who cannot join
- Diagnosis of chronic kidney disease (CKD) at baseline (glomerular filtration rate <60 mL/min/1.73m2, determined by chart review of either formal glomerular filtration rate testing, 24 hour creatinine creatinine clearance of age-appropriate serum creatinine-based estimated glomerular filtration rate equations; past kidney transplant)
- Previous use of any nephrotoxic drugs included on the provided Excluded Nephrotoxic Medications list in the two weeks prior to initiation of CisP treatment
- Previous use of CisP
- Previous radiotherapy (total body irradiation or abdominal radiation only) in the last 1 month prior to study
- Previous hematopoietic stem cell transplant
- Any chronic or acute health condition that the investigator feels would render the patient inappropriate for this study, including but not limited to significant uncontrolled cardiorespiratory, hepatic, infectious, or renal disease at the discretion of the investigator
Trial locations and contacts
1 site in 1 country. Contact the study team or a site near you to ask about taking part.
Canada1 site, 1 recruiting
- Recruiting
London Health Sciences Centre
London, Ontario, N6A 5W9
Kathie Baer, MSc, (519) 685-8500 ext. 54524, kathie.baer@lhsc.on.ca
Robin Sachdeva, PhD, Robin.Sachdeva@lhsc.on.ca
About this study
Official title: A Canadian Study of Cisplatin mEtabolomics and NephroToxicity
Cisplatin (CisP) is a chemotherapeutic agent used to treat head and neck and lung cancer in adults and over 15 different pediatric cancers. Despite its known toxicity, CisP is still widely used as a first line chemotherapy as it is so effective. Nephrotoxicity is one of the most common adverse effects of CisP, occurring in 20-50% of patients. It manifests as acute kidney injury (AKI) typically within the first few days of exposure and is associated with short and long-term morbidity. Furthermore, AKI diagnosis is only possible once kidney damage has progressed to functional impairment, when mitigation strategies are ineffective. Tests that could predict AKI risk pre-emptively or diagnose early-stage AKI before functional loss would be very impactful, affording opportunities for prevention or early intervention to mitigate CisP nephrotoxicity, reduce morbidity and improve health outcomes.
The field of metabolomics seeks to identify patterns of small molecules (metabolites) involved in cell or tissue metabolism related to disease states, or patient factors like lifestyle and genetics. Plasma and urine are ideal for sampling the metabolome, which can identify at-risk patients and reveal disease-related changes earlier than existing diagnostic methods do.
In CisP-treated children and adults from across Canada, we will identify urine and plasma metabolite profiles a) prior to CisP dosing that predict CisP AKI risk, and b) shortly after dosing to identify early-stage nephrotoxicity, before clinical signs of AKI are detectable. Our identified biomarkers will allow individualization of CisP treatment based on the level of nephrotoxicity risk and the design of trials to mitigate the progression and complications of CisP nephrotoxicity.
- Conditions
- Acute Kidney Injury, Cancer
- Being tested
- Questionnaire, sampling of blood, urine and saliva
- Medical subject headings
- Acute Kidney Injury, Neoplasms
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
Questionnaire, sampling of blood, urine and salivaOther
We are following patients who are receiving Cisplatin as part of their cancer therapy.
| Study group | Role | What they receive |
|---|---|---|
| Adults receiving Cisplatin as part of their cancer therapy | Not described Receives: Other: Questionnaire, sampling of blood, urine and saliva | |
| Children receiving Cisplatin as part of their cancer therapy | Not described Receives: Other: Questionnaire, sampling of blood, urine and saliva |
What is being measured
The primary outcome is the main question the study is designed to answer.
To identify patterns of metabolites and specific metabolites prior to and shortly after CisP treatment that predict AKI risk and identify the onset of AKI early (discovery cohort).
Measured: 8+ years
Secondary outcomes (1)
To independently validate our findings and develop a precision medicine algorithm using metabolites to predict patients at high risk for developing CisP AKI (validation cohort).
Measured: 8+ years
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted22 Jun 2020
- Study start12 Aug 2020
- Primary completion1 Apr 2026 (estimated)
- Study completion31 Dec 2028 (estimated)
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.
- 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
- Observational
- Observational model
- Cohort
- Time perspective
- Prospective
- Enrolment
- 600 participants (estimated)
Sponsor and investigators
- Lead sponsor
- The Hospital for Sick Children
- Sponsor type
- University, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), London Health Sciences Centre, Provincial Health Services Authority British Columbia
- Responsible party
- Principal investigator, Michael Zappitelli, The Hospital for Sick Children
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT04442516
- Sponsor's protocol ID
- CisP Metabolomics
- Acronym
- ACCENT
- Status last verified
- Apr 2024
- First submitted
- 18 Jun 2020
- Last updated
- 17 Apr 2024
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- Undecided
Publications
Jain A, Huang R, Lee J, Jawa N, Lim YJ, Guron M, Abish S, Boutros PC, Brudno M, Carleton B, Cuvelier GDE, Gunaratnam L, Ho C, Adeli K, Kuruvilla S, Lajoie G, Liu G, Nathan PC, Rod Rassekh S, Rieder M, Waikar SS, Welch SA, Weir MA, Winquist E, Wishart DS, Zorzi AP, Blydt-Hansen T, Zappitelli M, Urquhart B. A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol. Can J Kidney Health Dis. 2021 Nov 17;8:20543581211057708. doi: 10.1177/20543581211057708. eCollection 2021.
PubMed 34820133
Study at a glance
From the registry record, last updated by the sponsor on 17 Apr 2024. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- A Canadian Study of Cisplatin mEtabolomics and NephroToxicity
- ClinicalTrials.gov ID
- NCT04442516
- Acronym / sponsor ID
- ACCENT / CisP Metabolomics
- Conditions
- Acute Kidney Injury, Cancer
- Study type
- Observational
- Recruitment status
- Recruiting
- Enrolment
- 600 participants (estimated)
- Lead sponsor
- The Hospital for Sick ChildrenUniversity, hospital or other
- Collaborators
- Canadian Institutes of Health Research (CIHR), London Health Sciences Centre, Provincial Health Services Authority British Columbia
- Study start
- 12 Aug 2020 (actual)
- Primary completion
- 1 Apr 2026 (estimated)
- Study completion
- 31 Dec 2028 (estimated)
- First posted
- 22 Jun 2020 (actual)
- 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.
Cisplatin (CisP) is a chemotherapeutic agent used to treat head and neck and lung cancer in adults and over 15 different pediatric cancers. Despite its known toxicity, CisP is still widely used as a first line chemotherapy as it is so effective. Nephrotoxicity is one of the most common adverse effects of CisP, occurring in 20-50% of patients. It manifests as acute kidney injury (AKI) typically within the first few days of exposure and is associated with short and long-term morbidity. Furthermore, AKI diagnosis is only possible once kidney damage has progressed to functional impairment, when mitigation strategies are ineffective. Tests that could predict AKI risk pre-emptively or diagnose early-stage AKI before functional loss would be very impactful, affording opportunities for prevention or early intervention to mitigate CisP nephrotoxicity, reduce morbidity and improve health outcomes.
The field of metabolomics seeks to identify patterns of small molecules (metabolites) involved in cell or tissue metabolism related to disease states, or patient factors like lifestyle and genetics. Plasma and urine are ideal for sampling the metabolome, which can identify at-risk patients and reveal disease-related changes earlier than existing diagnostic methods do.
In CisP-treated children and adults from across Canada, we will identify urine and plasma metabolite profiles a) prior to CisP dosing that predict CisP AKI risk, and b) shortly after dosing to identify early-stage nephrotoxicity, before clinical signs of AKI are detectable. Our identified biomarkers will allow individualization of CisP treatment based on the level of nephrotoxicity risk and the design of trials to mitigate the progression and complications of CisP nephrotoxicity.
Study design
- Observational model
- Cohort
- Time perspective
- Prospective
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| Adults receiving Cisplatin as part of their cancer therapy | – | Other: Questionnaire, sampling of blood, urine and saliva |
| Children receiving Cisplatin as part of their cancer therapy | – | Other: Questionnaire, sampling of blood, urine and saliva |
Who may qualify
- Ages
- 3 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
- Study population
- Child Cohort. We already performed these study procedures on 159 children in the "ABLE" study, a 12-centre cohort study.Eligibility criteria and data/samples collected on these patients during their initial CisP treatment are almost identical to the present study. The cohort diagnoses include neuroblastoma, medulloblastoma, osteosarcoma, germ cell tumour, hepatoblastoma, and other cancers. Data and specimens from the pediatric study subjects in the ABLE study who were recruited during their first CisP infusion (about half) will be included in the current study. The remaining children (to reach a target of 300) will be recruited over 3 years from the following centres: McGill, UBC, SickKids, U. Manitoba and UWO. Adult Cohort. 300 adults (18 years of age or older) initiating CisP (≥75 mg/m2) treatment for head/neck or lung cancers will be recruited to participate in this study from PMH (Toronto), UBC and UWO over 2 years. Over 500 new patients/year are available across all sites.
Key inclusion criteria (3 listed)
- Adult participants: Initiating treatment with CisP (≥75 mg/m2) for head/neck or lung cancers at one of the Adult participating sites; 18 years of age or older.
- Paediatric participants: Initiating treatment with CisP for any cancer diagnosis at one of the Pediatric participating sites; greater than 3 months of age.
- All participants: Consent to participate in the study.
Key exclusion criteria (6 listed)
- Diagnosis of chronic kidney disease (CKD) at baseline (glomerular filtration rate <60 mL/min/1.73m2, determined by chart review of either formal glomerular filtration rate testing, 24 hour creatinine creatinine clearance of age-appropriate serum creatinine-based estimated glomerular filtration rate equations; past kidney transplant)
- Previous use of any nephrotoxic drugs included on the provided Excluded Nephrotoxic Medications list in the two weeks prior to initiation of CisP treatment
- Previous use of CisP
- Previous radiotherapy (total body irradiation or abdominal radiation only) in the last 1 month prior to study
- Previous hematopoietic stem cell transplant
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 |
|---|---|---|
| Questionnaire, sampling of blood, urine and salivaWe are following patients who are receiving Cisplatin as part of their cancer therapy. | Other | Adults receiving Cisplatin as part of their cancer therapy, Children receiving Cisplatin as part of their cancer therapy |
Primary outcome
To identify patterns of metabolites and specific metabolites prior to and shortly after CisP treatment that predict AKI risk and identify the onset of AKI early (discovery cohort).
Time frame: 8+ years
1 secondary outcome
To independently validate our findings and develop a precision medicine algorithm using metabolites to predict patients at high risk for developing CisP AKI (validation cohort).
Time frame: 8+ years
Results and safety
This study is still under way. Results are not available in the source record yet.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 17 Apr 2024.
- Derived from this study: PubMed 34820133Jain A, Huang R, Lee J, Jawa N, Lim YJ, Guron M, Abish S, Boutros PC, Brudno M, Carleton B, Cuvelier GDE, Gunaratnam L, Ho C, Adeli K, Kuruvilla S, Lajoie G, Liu G, Nathan PC, Rod Rassekh S, Rieder M, Waikar SS, Welch SA, Weir MA, Winquist E, Wishart DS, Zorzi AP, Blydt-Hansen T, Zappitelli M, Urquhart B. A Canadian Study of Cisplatin Metabolomics and Nephrotoxicity (ACCENT): A Clinical Research Protocol. Can J Kidney Health Dis. 2021 Nov 17;8:20543581211057708. doi: 10.1177/20543581211057708. eCollection 2021.
- 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.
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
An observational study of Acute Kidney Injury and Cancer, run by The Hospital for Sick Children at 1 site in Canada.
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 3 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: looking for participants now, as of the sponsor's last update on 17 Apr 2024. 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 Canada. 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.
Are results available for this study?
This study is still under way. Results are not available in the source record yet.
How can a doctor refer a patient or contact the research team?
Contact Michael Zappitelli, MD (416-813-7654 ext. 304077, michael.zappitelli@sickkids.ca), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
To identify patterns of metabolites and specific metabolites prior to and shortly after CisP treatment that predict AKI risk and identify the onset of AKI early (discovery cohort). (time frame: 8+ 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 NCT04442516, 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 17 Apr 2024.