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Trial record 16 of 16 for:    "Ependymoma" | "Folic Acid Antagonists"

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

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ClinicalTrials.gov Identifier: NCT00570817
Recruitment Status : Completed
First Posted : December 11, 2007
Last Update Posted : November 7, 2011
Sponsor:
Collaborators:
ML Jørgensen og Gunnar Hansens Foundation
Danish Child Cancer Foundation
Information provided by (Responsible Party):
University of Aarhus

Tracking Information
First Submitted Date  ICMJE December 10, 2007
First Posted Date  ICMJE December 11, 2007
Last Update Posted Date November 7, 2011
Study Start Date  ICMJE June 2007
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Current Primary Outcome Measures  ICMJE
 (submitted: December 10, 2007)
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. ]
Original Primary Outcome Measures  ICMJE Same as current
Change History Complete list of historical versions of study NCT00570817 on ClinicalTrials.gov Archive Site
Current Secondary Outcome Measures  ICMJE
 (submitted: December 10, 2007)
  • 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. ]
  • Days of hospitalization in relation to the methotrexate infusion. [ Time Frame: 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. ]
  • Drug exposure measured by area under the curve. [ Time Frame: 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. ]
  • Total dosage of leucovorin. [ Time Frame: From initiation of the methotrexate infusion and til serum methotrexate concentration is below 0,2 micromol/l. ]
Original Secondary Outcome Measures  ICMJE Same as current
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE Prevention of Methotrexate Induced Nephrotoxicity and Prolonged Drug Elimination Time With 12 Hours Prehydration
Official Title  ICMJE Nephrotoxicity Induced by High-Dose Methotrexate Infusions to Children With Malignant Diseases
Brief Summary 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.
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  ICMJE Interventional
Study Phase  ICMJE Not Applicable
Study Design  ICMJE Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)
Primary Purpose: Prevention
Condition  ICMJE Methotrexate Induced Nephrotoxicity
Intervention  ICMJE 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.
Study Arms  ICMJE
  • 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.

    Intervention: Other: 12 hours of prehydration
  • 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.

    Intervention: Other: 12 hours of prehydration
Publications * Not Provided

*   Includes publications given by the data provider as well as publications identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.
 
Recruitment Information
Recruitment Status  ICMJE Completed
Actual Enrollment  ICMJE
 (submitted: January 10, 2011)
47
Original Estimated Enrollment  ICMJE
 (submitted: December 10, 2007)
100
Actual Study Completion Date  ICMJE October 2010
Actual Primary Completion Date October 2010   (Final data collection date for primary outcome measure)
Eligibility Criteria  ICMJE

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.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 1 Year to 21 Years   (Child, Adult)
Accepts Healthy Volunteers  ICMJE No
Contacts  ICMJE Contact information is only displayed when the study is recruiting subjects
Listed Location Countries  ICMJE Denmark
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00570817
Other Study ID Numbers  ICMJE 20070009
The Danish Data
Protection Agency 2007-41-0014
Has Data Monitoring Committee Yes
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Responsible Party University of Aarhus
Study Sponsor  ICMJE University of Aarhus
Collaborators  ICMJE
  • ML Jørgensen og Gunnar Hansens Foundation
  • Danish Child Cancer Foundation
Investigators  ICMJE
Study Director: Henrik Schrøder, MD
PRS Account University of Aarhus
Verification Date January 2011

ICMJE     Data element required by the International Committee of Medical Journal Editors and the World Health Organization ICTRP