Prevention of Methotrexate Induced Nephrotoxicity and Prolonged Drug Elimination Time With 12 Hours Prehydration

November 4, 2011 updated by: University of Aarhus

Nephrotoxicity Induced by High-Dose Methotrexate Infusions to Children With Malignant Diseases

Infusions with high-dose methotrexate 5 g/m2 or 8 g/m2 are used to treat children with acute lymphoblastic leukemia (ALL), non-Hodgkin's lymphoma, medulloblastoma and ependymoma. Methotrexate is primarily excreted unchanged by the kidney where it can course acute kidney damage resulting in prolonged time of excretion of the drug. Our main hypothesis is that 12 hours of intravenous hydration before the methotrexate infusion is more efficacious in preventing methotrexate induced kidney damage compared to four hours of hydration.

Study Overview

Status

Status

Indicates the current recruitment status or the expanded access status.
Completed

Conditions

Conditions

The disease, disorder, syndrome, illness, or injury that is being studied. On ClinicalTrials.gov, conditions may also include other health-related issues, such as lifespan, quality of life, and health risks.

Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.

Detailed Description

Infusions with high-dose methotrexate 5 g/m2 or 8 g/m2 are according to the protocol of the Nordic Association for Pediatric Hematology and Oncology 2000 (NOPHO-2000) used to treat children with acute lymphoblastic leukemia (ALL). Treatment with methotrexate 5 g/m2 is also used to treat children with non-Hodgkin lymphoma, medulloblastoma and ependymoma. Methotrexate is primarily excreted unchanged by the kidney where it can course acute nephrotoxicity resulting in prolonged elimination time of the drug. Data from a 10 years retrospective investigation at our pediatric unit show, that in spite of urine alkalinization and intensive hydration the elimination of methotrexate is prolonged in 20-50% of the infusions. The long exposure of a high serum methotrexate concentration is associated with an increased frequency of mucositis and bone marrow suppression. Further more the need of rescue with folic acid is problematic, because it is possibly that it can result in a higher risk of relapse of ALL (Leukemia 2006; Skarby TV). Most ALL protocols prescribe prehydration of 2-6 hours before initiation of the methotrexate infusion and it has never been investigated in a randomized controlled trail if a longer time of prehydration can prevent nephrotoxicity and reduce the risk of prolonged elimination. In our pediatric unit the prehydration is given with a rate of 150 ml/m2/hour with a solution of 5% glucose with 40 mmol sodium bicarbonate/L and 20 mmol potassium chloride/L.

Our main hypothesis is that 12 hours of prehydration is more efficacious in preventing methotrexate induced nephrotoxicity compared to four hours of prehydration. A child enrolled in the study will before half of the methotrexate infusions receive 12 hours of prehydration and before the other half it will receive four hours of prehydration.

Study Type

Study Type

Describes the nature of a clinical study. Study types include interventional studies (also called clinical trials), observational studies (including patient registries), and expanded access.
Interventional

Enrollment (Actual)

Enrollment

The number of participants in a clinical study. The "anticipated" enrollment is the target number of participants that the researchers need for the study.
47

Phase

Phase

The stage of a clinical trial studying a drug or biological product, based on definitions developed by the U.S. Food and Drug Administration (FDA). The phase is based on the study's objective, the number of participants, and other characteristics. There are five phases: Early Phase 1 (formerly listed as Phase 0), Phase 1, Phase 2, Phase 3, and Phase 4. Not Applicable is used to describe trials without FDA-defined phases, including trials of devices or behavioral interventions.
  • Not Applicable

Contacts and Locations

This section provides the contact details for those conducting the study, and information on where this study is being conducted.

Study Locations

  • Denmark
    • Aarhus N
      • Aarhus, Aarhus N, Denmark, 8200
        • Aarhus University Hospital, Skejby

Participation Criteria

Researchers look for people who fit a certain description, called eligibility criteria. Some examples of these criteria are a person's general health condition or prior treatments.

Eligibility Criteria

Eligibility Criteria

The key requirements that people who want to participate in a clinical study must meet or the characteristics they must have. Eligibility criteria consist of both inclusion criteria (which are required for a person to participate in the study) and exclusion criteria (which prevent a person from participating). Types of eligibility criteria include whether a study accepts healthy volunteers, has age or age group requirements, or is limited by sex.

Ages Eligible for Study

1 year to 21 years (Child, Adult)

Accepts Healthy Volunteers

No

Genders Eligible for Study

All

Description

Inclusion Criteria:

  • Age between 1 and 21 years at the diagnosis of ALL
  • Treatment with high-dose methotrexate 5 g/m2 or 8 g/m2 according to the protocol "Nordic Association for Pediatric Hematology and Oncology 2000 (NOPHO-2000)" or the new protocol (NOPHO-2008) to which enrolment begin approx. January 2009.
  • Treatment with high-dose methotrexate 5 g/m2 according to the protocol "Treatment Protocol for T-Cell and B-Precursor Cell Lymphoblastic Lymphoma 2002 of the European Inter-group Co-operation on Childhood Non-Hodgkin-Lymphoma (EICNHL)"
  • Treatment of medulloblastoma and ependymoma with high-dose methotrexate 5 g/m2 according to the protocol: "(HIT2000)Hirntumorprotokoll der Hrbeitsgruppe für Hirntumoren" from Deutsche Gesellschaft für Pädiatrische Onkologie und Hämatologie (GPOH).

Exclusion Criteria:

  • Patient or parents not willing to give consent.

Study Plan

This section provides details of the study plan, including how the study is designed and what the study is measuring.

How is the study designed?

Design Details

  • Primary Purpose: Prevention
  • Allocation: Randomized
  • Interventional Model: Crossover Assignment
  • Masking: None (Open Label)

Arms and Interventions

Participant Group / Arm

Participant Group / Arm

A group or subgroup of participants in a clinical trial that receives a specific intervention/treatment, or no intervention, according to the trial's protocol.
Intervention / Treatment

Intervention / Treatment

A process or action that is the focus of a clinical study. Interventions include drugs, medical devices, procedures, vaccines, and other products that are either investigational or already available. Interventions can also include noninvasive approaches, such as education or modifying diet and exercise.
Other: 1

The child will receive prehydration at the methotrexate infusions in the following order:

At the 1st methotrexate infusion the child will receive 4 hours prehydration. At the 2nd methotrexate infusion the child will receive 12 hours prehydration. At the 3rd methotrexate infusion the child will receive 4 hours prehydration. At the 4th methotrexate infusion the child will receive 12 hours prehydration. At the 5th methotrexate infusion the child will receive 4 hours prehydration. At the 6th methotrexate infusion the child will receive 12 hours prehydration. At the 7th methotrexate infusion the child will receive 4 hours prehydration. At the 8th methotrexate infusion the child will receive 12 hours prehydration.
Other: 12 hours of prehydration
12 hours of prehydration with an infusion rate of 150 ml/m2/hour with a solution of 5% glucose with 40 mmol sodium bicarbonate/L and 20 mmol potassium chloride/L.
Other: 2

The child will receive prehydration at the methotrexate infusions in the following order:

At the 1st methotrexate infusion the child will receive 12 hours prehydration. At the 2nd methotrexate infusion the child will receive 4 hours prehydration. At the 3rd methotrexate infusion the child will receive 12 hours prehydration. At the 4th methotrexate infusion the child will receive 4 hours prehydration. At the 5th methotrexate infusion the child will receive 12 hours prehydration. At the 6th methotrexate infusion the child will receive 4 hours prehydration. At the 7th methotrexate infusion the child will receive 12 hours prehydration. At the 8th methotrexate infusion the child will receive 4 hours prehydration.
Other: 12 hours of prehydration
12 hours of prehydration with an infusion rate of 150 ml/m2/hour with a solution of 5% glucose with 40 mmol sodium bicarbonate/L and 20 mmol potassium chloride/L.

What is the study measuring?

Primary Outcome Measures

Primary Outcome Measures

In a clinical study's protocol, the planned outcome measure that is the most important for evaluating the effect of an intervention/treatment. Most clinical studies have one primary outcome measure, but some have more than one.
Outcome Measure
Time Frame
Prolonged methotrexate elimination time, defined by serum methotrexate concentrations: > 3,0 micromol/L at 36 hours; > 1,0 micromol/L at 42 hours or > 0,2 micromol/L at 66 hours after initiation of the methotrexate infusion.
Time Frame: From 36-66 hours after the initiation of methotrexate infusion.
From 36-66 hours after the initiation of methotrexate infusion.

Secondary Outcome Measures

Secondary Outcome Measures

In a clinical study's protocol, a planned outcome measure that is not as important as the primary outcome measure for evaluating the effect of an intervention but is still of interest. Most clinical studies have more than one secondary outcome measure.
Outcome Measure
Time Frame
Development of methotrexate induced nephropathy, defined by an increase in serum creatinine by 50% or more compared with the serum creatinine concentration before start of each methotrexate infusion.
Time Frame: From the initiation of methotrexate infusion until 66 hours after.
From the initiation of methotrexate infusion until 66 hours after.
Days of hospitalization in relation to the methotrexate infusion.
Time Frame: Days in relation to the methotrexate infusion and side effects.
Days in relation to the methotrexate infusion and side effects.
Difference in baseline creatinine to highest serum creatinine between groups.
Time Frame: From initiation of the methotrexate infusion and up til 14 days after.
From initiation of the methotrexate infusion and up til 14 days after.
Drug exposure measured by area under the curve.
Time Frame: From 23 hours til 66 hours after initiation of the methotrexate infusion.
From 23 hours til 66 hours after initiation of the methotrexate infusion.
Duration and degree of side effects to the methotrexate treatment.
Time Frame: From initiation of the methotrexate infusion and up til on month after.
From initiation of the methotrexate infusion and up til on month after.
Total dosage of leucovorin.
Time Frame: From initiation of the methotrexate infusion and til serum methotrexate concentration is below 0,2 micromol/l.
From initiation of the methotrexate infusion and til serum methotrexate concentration is below 0,2 micromol/l.

Collaborators and Investigators

This is where you will find people and organizations involved with this study.

Sponsor

Sponsor

The organization or person who initiates the study and who has authority and control over the study.
University of Aarhus

Collaborators

Collaborators

An organization other than the sponsor that provides support for a clinical study. This support may include activities related to funding, design, implementation, data analysis, or reporting.
Danish Child Cancer Foundation
ML Jørgensen og Gunnar Hansens Foundation

Investigators

Investigators

A researcher involved in a clinical study. Related terms include site principal investigator, site sub-investigator, study chair, study director, and study principal investigator.
  • Study Director: Henrik Schrøder, MD

Study record dates

These dates track the progress of study record and summary results submissions to ClinicalTrials.gov. Study records and reported results are reviewed by the National Library of Medicine (NLM) to make sure they meet specific quality control standards before being posted on the public website.

Study Major Dates

Study Start

Study Start

The actual date on which the first participant was enrolled in a clinical study. The "anticipated" study start date is the date that the researchers think will be the study start date.
June 1, 2007

Primary Completion (Actual)

Primary Completion

The date on which the last participant in a clinical study was examined or received an intervention to collect final data for the primary outcome measure. Whether the clinical study ended according to the protocol or was terminated does not affect this date. For clinical studies with more than one primary outcome measure with different completion dates, this term refers to the date on which data collection is completed for all the primary outcome measures. The "anticipated" primary completion date is the date that the researchers think will be the primary completion date for the study.
October 1, 2010

Study Completion (Actual)

Study Completion

The date on which the last participant in a clinical study was examined or received an intervention/treatment to collect final data for the primary outcome measures, secondary outcome measures, and adverse events (that is, the last participant's last visit). The "anticipated" study completion date is the date that the researchers think will be the study completion date.
October 1, 2010

Study Registration Dates

First Submitted

First Submitted

The date on which the study sponsor or investigator first submitted a study record to ClinicalTrials.gov. There is typically a delay of a few days between the first submitted date and the record's availability on ClinicalTrials.gov (the first posted date).
December 10, 2007

First Submitted That Met QC Criteria

First Submitted That Met QC Criteria

The date on which the study sponsor or investigator first submits a study record that is consistent with National Library of Medicine (NLM) quality control (QC) review criteria. The sponsor or investigator may need to revise and submit a study record one or more times before NLM's QC review criteria are met. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
December 10, 2007

First Posted (Estimate)

First Posted

The date on which the study record was first available on ClinicalTrials.gov after National Library of Medicine (NLM) quality control (QC) review has concluded. There is typically a delay of a few days between the date the study sponsor or investigator submitted the study record and the first posted date.
December 11, 2007

Study Record Updates

Last Update Posted (Estimate)

Last Update Posted

The most recent date on which changes to a study record were made available on ClinicalTrials.gov. There may be a delay between when the changes were submitted to ClinicalTrials.gov by the study's sponsor or investigator (the last update submitted date) and the last update posted date.
November 6, 2011

Last Update Submitted That Met QC Criteria

Last Update Submitted That Met QC Criteria

The most recent date on which the study sponsor or investigator submitted changes to a study record that are consistent with National Library of Medicine (NLM) quality control (QC) review criteria. It is the responsibility of the sponsor or investigator to ensure that the study record is consistent with the NLM QC review criteria.
November 4, 2011

Last Verified

Last Verified

The most recent date on which the study sponsor or investigator confirmed the information about a clinical study on ClinicalTrials.gov as accurate and current. If a study with a recruitment status of recruiting; not yet recruiting; or active, not recruiting has not been confirmed within the past 2 years, the study's recruitment status is shown as unknown.
January 1, 2011

More Information

Terms related to this study

Keywords

Other Study ID Numbers

Other Study ID Numbers

Identifiers or ID numbers other than the NCT number that are assigned to a clinical study by the study's sponsor, funders, or others. These numbers may include unique identifiers from other trial registries and National Institutes of Health grant numbers.
  • 20070009
  • The Danish Data
  • Protection Agency 2007-41-0014

This information was retrieved directly from the website clinicaltrials.gov without any changes. If you have any requests to change, remove or update your study details, please contact register@clinicaltrials.gov. As soon as a change is implemented on clinicaltrials.gov, this will be updated automatically on our website as well.

Clinical Trials on Methotrexate Induced Nephrotoxicity

Clinical Trials on 12 hours of prehydration

Search Similar Trials

Sponsors and Collaborators

Medical Conditions

Drug Interventions

Conditions

Rare Diseases

Drug Interventions

Dietary Supplements

Sponsor/Collaborators

Locations

Cookie Settings

We use cookies to ensure that we give you the best experience on our website. For more details carefully read our Privacy and Cookies Policy. ...>>>You can change your preferences or withdraw your consent at any time by deleting the cookies from your website or computer as described in the policy. Please accept it and choose your preferences by ticking the corresponding boxes in the "Manage Settings" section below. Please carefully read our Terms of Service before you proceed with using any part of this website.
«Manage Settings