Clinical Trials Logo

Clinical Trial Details — Status: Completed

Administrative data

NCT number NCT00001108
Other study ID # P1007
Secondary ID 11643ACTG P1007P
Status Completed
Phase Phase 1
First received
Last updated
Est. completion date June 2000

Study information

Verified date October 2021
Source National Institute of Allergy and Infectious Diseases (NIAID)
Contact n/a
Is FDA regulated No
Health authority
Study type Interventional

Clinical Trial 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.


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.


Recruitment information / eligibility

Status Completed
Enrollment 6
Est. completion date June 2000
Est. primary completion date
Accepts healthy volunteers No
Gender All
Age group 4 Years to 22 Years
Eligibility 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.

Study Design


Related Conditions & MeSH terms


Intervention

Drug:
Ritonavir

Nelfinavir mesylate

Saquinavir

Nevirapine

Lamivudine

Stavudine

Didanosine


Locations

Country Name City State
United States Johns Hopkins Hosp - Pediatric Baltimore Maryland
United States Univ of Alabama at Birmingham - Pediatric Birmingham Alabama
United States Children's Hosp of Boston Boston Massachusetts
United States Chicago Children's Memorial Hosp Chicago Illinois
United States Cook County Hosp Chicago Illinois
United States North Shore Univ Hosp Great Neck New York
United States Univ of Mississippi Med Ctr Jackson Mississippi
United States UCLA Med Ctr / Pediatric Los Angeles California
United States Saint Jude Children's Research Hosp of Memphis Memphis Tennessee
United States Univ of Miami (Pediatric) Miami Florida
United States Tulane Univ / Charity Hosp of New Orleans New Orleans Louisiana
United States Bellevue Hosp / New York Univ Med Ctr New York New York
United States Columbia Presbyterian Med Ctr New York New York
United States Incarnation Children's Ctr / Columbia Presbyterian Med Ctr New York New York
United States Univ of Medicine & Dentistry of New Jersey / Univ Hosp Newark New Jersey
United States Sacred Heart Children's Hosp / CMS of Florida Pensacola Florida
United States Med College of Virginia Richmond Virginia
United States SUNY Health Sciences Ctr at Syracuse / Pediatrics Syracuse New York
United States Univ of Massachusetts Med School Worcester Massachusetts

Sponsors (2)

Lead Sponsor Collaborator
National Institute of Allergy and Infectious Diseases (NIAID) Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD)

Country where clinical trial is conducted

United States, 

See also
  Status Clinical Trial Phase
Completed NCT05454514 - Automated Medication Platform With Video Observation and Facial Recognition to Improve Adherence to Antiretroviral Therapy in Patients With HIV/AIDS N/A
Completed NCT03760458 - The Pharmacokinetics, Safety, and Tolerability of Abacavir/Dolutegravir/Lamivudine Dispersible and Immediate Release Tablets in HIV-1-Infected Children Less Than 12 Years of Age Phase 1/Phase 2
Completed NCT03141918 - Effect of Supplementation of Bioactive Compounds on the Energy Metabolism of People Living With HIV / AIDS N/A
Completed NCT03067285 - A Phase IV, Open-label, Randomised, Pilot Clinical Trial Designed to Evaluate the Potential Neurotoxicity of Dolutegravir/Lamivudine/Abacavir in Neurosymptomatic HIV Patients and Its Reversibility After Switching to Elvitegravir/Cobicistat/Emtricitabine/Tenofovir Alafenamide. DREAM Study Phase 4
Recruiting NCT04579146 - Coronary Artery Disease (CAD) in Patients HIV-infected
Completed NCT06212531 - Papuan Indigenous Model of Male Circumcision N/A
Active, not recruiting NCT03256422 - Antiretroviral Treatment Taken 4 Days Per Week Versus Continuous Therapy 7/7 Days Per Week in HIV-1 Infected Patients Phase 3
Completed NCT03256435 - Retention in PrEP Care for African American MSM in Mississippi N/A
Completed NCT00517803 - Micronutrient Supplemented Probiotic Yogurt for HIV/AIDS and Other Immunodeficiencies N/A
Active, not recruiting NCT03572335 - Systems Biology of Diffusion Impairment in Human Immunodeficiency Virus (HIV)
Completed NCT04165200 - Fecal Microbiota Transplantation as a Therapeutic Strategy for Patients Infected With HIV N/A
Recruiting NCT03854630 - Hepatitis B Virus Vaccination in HIV-positive Patients and Individuals at High Risk for HIV Infection Phase 4
Terminated NCT03275571 - HIV, Computerized Depression Therapy & Cognition N/A
Completed NCT02234882 - Study on Pharmacokinetics Phase 1
Completed NCT01618305 - Evaluating the Response to Two Antiretroviral Medication Regimens in HIV-Infected Pregnant Women, Who Begin Antiretroviral Therapy Between 20 and 36 Weeks of Pregnancy, for the Prevention of Mother-to-Child Transmission Phase 4
Recruiting NCT05043129 - Safety and Immune Response of COVID-19 Vaccination in Patients With HIV Infection
Not yet recruiting NCT05536466 - The Influence of Having Bariatric Surgery on the Pharmacokinetics, Safety and Efficacy of the Novel Non-nucleoside Reverse Transcriptase Inhibitor Doravirine N/A
Recruiting NCT04985760 - Evaluation of Trimer 4571 Therapeutic Vaccination in Adults Living With HIV on Suppressive Antiretroviral Therapy Phase 1
Completed NCT05916989 - Stimulant Use and Methylation in HIV
Terminated NCT02116660 - Evaluation of Renal Function, Efficacy, and Safety When Switching From Tenofovir/Emtricitabine Plus a Protease Inhibitor/Ritonavir, to a Combination of Raltegravir (MK-0518) Plus Nevirapine Plus Lamivudine in HIV-1 Participants With Suppressed Viremia and Impaired Renal Function (MK-0518-284) Phase 2