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A Study of the Safety and Effectiveness of Treating Advanced AIDS Patients Between Ages 4 and 22 With 7 Drugs, Some at Higher Than Usual Doses

The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
 
ClinicalTrials.gov Identifier: NCT00001108
Recruitment Status : Completed
First Posted : August 31, 2001
Last Update Posted : November 1, 2021
Sponsor:
Collaborator:
Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Information provided by (Responsible Party):
National Institute of Allergy and Infectious Diseases (NIAID)

Tracking Information
First Submitted Date  ICMJE November 2, 1999
First Posted Date  ICMJE August 31, 2001
Last Update Posted Date November 1, 2021
Study Start Date  ICMJE Not Provided
Primary Completion Date Not Provided
Current Primary Outcome Measures  ICMJE Not Provided
Original Primary Outcome Measures  ICMJE Not Provided
Change History
Current Secondary Outcome Measures  ICMJE Not Provided
Original Secondary Outcome Measures  ICMJE Not Provided
Current Other Pre-specified Outcome Measures Not Provided
Original Other Pre-specified Outcome Measures Not Provided
 
Descriptive Information
Brief Title  ICMJE A Study of the Safety and Effectiveness of Treating Advanced AIDS Patients Between Ages 4 and 22 With 7 Drugs, Some at Higher Than Usual Doses
Official Title  ICMJE Multi-Drug Antiretroviral Therapy for Heavily Pretreated Pediatric AIDS Patients: A Phase I Proof of Concept Trial
Brief Summary

The purpose of this study is to see if 7 drugs, some of them given at higher doses than normal, are safe and tolerated by young patients with AIDS who have failed to respond to other treatments. The study will also see what effect taking several anti-HIV drugs together at high doses has on the body's ability to fight HIV infection. The 7 drugs that will be given in this study are stavudine (d4T), didanosine (ddI), lamivudine (3TC), nelfinavir (NFV), ritonavir (RTV), saquinavir (SQV), and nevirapine (NVP).

(This study has been changed from an 8-drug regimen to a 7-drug regimen. Patients no longer receive the drug hydroxyurea [HU].) Doctors are seeing many HIV-positive children who did not get good long-term results from the current anti-HIV drugs. Some doctors believe anti-HIV drugs fail because drug levels in the body are too low. In this study, doctors will give patients 7 drugs, some at higher doses than normal. Since it is very important that patients on the study take all of these drugs, doctors will make it as easy as possible. Doctors want to try this because children with advanced AIDS have few treatment choices.

Detailed Description

Clinicians are increasingly confronted with HIV-positive children who have failed all available antiretroviral therapies and have few viable treatment options. Virologic failure in these patients may be a result of antiretroviral resistance, likely a result of poor adherence to the treatment regimen or inadequate dosing. This study is designed to achieve adherence through observation of drug administration for the first 8 weeks of the study and to further overcome resistance by intensive, high-dose, multi-drug therapy. Treatment with more than 4 drugs has not been studied formally in children, but pediatricians caring for children with AIDS have used such strategies off study with success. Dose intensification may also aid in overcoming resistance; therefore, in this trial, d4T, 3TC, and NFV are administered at up to twice their standard doses. Given the limited therapeutic options available to HIV-positive children with poor prognoses, high-dose, multi-drug therapy merits study. [AS PER AMENDMENT 01/07/00: Pancreatitis, which may be fatal in some cases, has occurred during therapy with ddI. The risk of pancreatitis may be increased when ddI is used in combination with HU. ACTG A5025, a study that had a d4T/ddI/HU arm, was terminated because of significant toxicity concerns related to the HU-containing arm. Patients enrolled in ACTG P1007 may be at increased risk of developing pancreatitis given their advanced disease state and the use of multiple drugs including HU. The study had been amended to address these concerns.] [AS PER AMENDMENT 12/19/01: HU has been removed from the drug regimen.]

Patient enrollment is staged to allow study physicians to aggressively monitor patients for signs of toxicity. Initially, patients are admitted to a hospital or clinical research center for 2 weeks, where they initiate an [AS PER AMENDMENT 12/19/01: "8-drug regimen" is replaced by "7-drug regimen"] and undergo frequent physical exams and blood tests to assess [AS PER AMENDMENT 12/19/01: glucose levels], pharmacokinetics, virologic response, and toxicity. If investigators identify important drug interactions requiring modification of the combination regimen, or if there are early regimen-terminating toxicities, the trial will be halted to address these concerns. After 2 weeks, the patient is discharged to return home. Study personnel visit the patient's house twice a day for 6 more weeks to observe drug administration, and the patient continues to receive regular physical exams and blood tests. At the end of Week 24, all patients with plasma RNA levels of 10,000 copies/ml or less are offered the opportunity to continue their regimen to Week 48. Patients with plasma RNA levels above 10,000 copies/ml at Week 24 and patients who experience virologic rebound at or after Week 24 are taken off study unless the patient's family and the investigator feel it is in the best interest of the child to remain on study. [AS PER AMENDMENT 12/19/01: The 2-week hospital or GCRC stay is no longer required. A 2-day stay in a hospital or GCRC for the purpose of drug regimen training is recommended, but not mandatory. Study personnel visit the patient once a day for 6 weeks at an agreed upon location or by phone contact.

Study Type  ICMJE Interventional
Study Phase  ICMJE Phase 1
Study Design  ICMJE Primary Purpose: Treatment
Condition  ICMJE HIV Infections
Intervention  ICMJE
  • Drug: Ritonavir
  • Drug: Nelfinavir mesylate
  • Drug: Saquinavir
  • Drug: Nevirapine
  • Drug: Lamivudine
  • Drug: Stavudine
  • Drug: Didanosine
Study Arms  ICMJE Not Provided
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
Enrollment  ICMJE
 (submitted: June 23, 2005)
6
Original Enrollment  ICMJE Same as current
Actual Study Completion Date  ICMJE June 2000
Primary Completion Date Not Provided
Eligibility Criteria  ICMJE

Inclusion Criteria

Patients may be eligible for this trial if they:

  • Are HIV-positive.
  • Have HIV levels of 10,000 copies/ml or more.
  • Are between ages 4 and 22.
  • Have motivation and ability to conform to the complex treatment regimen.
  • Agree to practice abstinence or use 2 effective methods of birth control during the study and until 3 months after stopping the study drugs, if sexually active.
  • Have written informed consent from a parent or legal guardian if under age 18.
  • Have used at least 3 different nucleoside reverse transcriptase inhibitors (NRTIs) for at least 3 months each or have shown resistance to at least 3 different NRTIs.
  • Have used at least 1 nonnucleoside reverse transcriptase inhibitor (NNRTI) for at least 3 months each or have shown resistance.
  • Have used at least 2 different courses of a protease inhibitor (PI)-containing regimen, each of which was at least 6 months, or have evidence of mutations to at least 2 different PIs.
  • This study has been changed. The inclusion criteria reflects a change in the prior anti-HIV therapy required, age requirement, and the required CD4 and HIV levels.

Exclusion Criteria

Patients will not be eligible for this trial if they:

  • Are allergic to even 1 study drug or have ever had to stop 1 of these drugs because of a bad reaction to it.
  • Have a history of diabetes, hepatitis C, hepatitis B, or certain diseases of the nervous system, heart, or pancreas.
  • Have had a serious infection within 14 days of starting the study.
  • Need certain drugs that interact with the study drugs. (See Technical Summary for more details.)
  • Are pregnant or breast-feeding.
  • Have had hepatitis within 30 days of study entry.
Sex/Gender  ICMJE
Sexes Eligible for Study: All
Ages  ICMJE 4 Years to 22 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 United States
Removed Location Countries  
 
Administrative Information
NCT Number  ICMJE NCT00001108
Other Study ID Numbers  ICMJE P1007
11643 ( Registry Identifier: DAIDS ES )
ACTG P1007
PACTG P1007
Has Data Monitoring Committee Not Provided
U.S. FDA-regulated Product Not Provided
IPD Sharing Statement  ICMJE Not Provided
Current Responsible Party National Institute of Allergy and Infectious Diseases (NIAID)
Original Responsible Party Not Provided
Current Study Sponsor  ICMJE National Institute of Allergy and Infectious Diseases (NIAID)
Original Study Sponsor  ICMJE Same as current
Collaborators  ICMJE Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)
Investigators  ICMJE
Study Chair: Grace Aldrovandi
Study Chair: Paul Palumbo
PRS Account National Institute of Allergy and Infectious Diseases (NIAID)
Verification Date October 2021

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