Therapeutic Response Evaluation and Adherence Trial (TREAT) (TREAT)
|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. Know the risks and potential benefits of clinical studies and talk to your health care provider before participating. Read our disclaimer for details.|
|ClinicalTrials.gov Identifier: NCT02286154|
Recruitment Status : Recruiting
First Posted : November 7, 2014
Last Update Posted : December 9, 2021
|Condition or disease||Intervention/treatment||Phase|
|Anemia, Sickle Cell||Drug: Hydroxyurea||Not Applicable|
There is now ample clinical evidence that hydroxyurea is a safe and effective medication for adults and children with sickle cell anemia (SCA), and most hematologists agree the short-term safety and efficacy of hydroxyurea has been proven. The National Heart, Lung, and Blood Institute have recently released evidence-based guidelines for SCA, recommending that hydroxyurea be offered to all affected children as young as nine months of age, regardless of clinical severity. Despite the overwhelming evidence demonstrating safety and efficacy, hydroxyurea remains underutilized for a variety of reasons. In this prospective study, the investigators will utilize innovative strategies designed to address and overcome some of the barriers that currently limit the use of hydroxyurea for children with SCA. The investigators will utilize novel laboratory techniques and pharmacometric modeling in order to accurately predict the most effective hydroxyurea dose referred to as the maximum tolerated dose. The investigators aim to develop a screening urine test to objectively and accurately determine adherence to hydroxyurea therapy. In addition, the study will document critical laboratory and clinical characteristics of this unique population of patients with SCA who begin hydroxyurea at a young age.
This study will follow two groups of patients. The first group, referred to as the New Cohort, will include mostly young infants who are not receiving hydroxyurea therapy upon entering the study. The starting dose of hydroxyurea for each of the participants in the New Cohort will be individually determined using the novel population PK/PD dose-prediction model. The second group of study participants, referred to as the Old Cohort, will include patients who are already receiving hydroxyurea therapy upon study entry. Both the Old and New Cohort (New Cohort) will be included in the development of a urine biomarker of adherence and will be followed throughout the study to document the effect hydroxyurea has upon organ function and quality of life. It is important to note that this is not a therapeutic drug trial. Prior to enrollment in the study, participants, along with their families and clinical providers, have decided to initiate hydroxyurea therapy for clinical indications. Except for the dose prediction model for the New Cohort, participants will be treated and monitored according to the routine clinical practice guidelines of the Cincinnati Children's Hospital Comprehensive Sickle Cell Center.
|Study Type :||Interventional (Clinical Trial)|
|Estimated Enrollment :||150 participants|
|Intervention Model:||Single Group Assignment|
|Masking:||None (Open Label)|
|Official Title:||Therapeutic Response Evaluation and Adherence Trial (TREAT): A Prospective Study of Hydroxyurea for Children With Sickle Cell Anemia|
|Study Start Date :||October 2014|
|Estimated Primary Completion Date :||October 2024|
|Estimated Study Completion Date :||October 2024|
All enrolled participants will receive hydroxyurea, but upon enrollment, participants will be identified as part of the "New Cohort" or "Old Cohort" "New Cohort" participants include those who are not receiving hydroxyurea therapy upon study entry. "Old Cohort" participants include those who are already receiving hydroxyurea therapy upon study entry. New Cohort participants will have starting dose predicted using PK/PD data and Old Cohort participants will continue dosing per clinical guidelines.
For New Cohort participants, PK/PD data will be used to predict the most effective maximum tolerated dose. Old Cohort participants will receive hydroxyurea escalated to MTD as per local clinical guidelines.
- Time to Reach Maximum Tolerated Dose (months) [ Time Frame: Twelve months ]Time it takes to reach maximum tolerated dose (MTD) of hydroxyurea quantified in months.
- Hydroxyurea adherence [ Time Frame: Monthly until MTD then yearly up to ten years ]Hydroxyurea adherence as measured by analysis of urine metabolites
- Neurological function [ Time Frame: Yearly ]Neurological function as measured by transcranial Doppler study (yearly), brain MRI (every 5 years beginning at age 5).
- Non-invasive Transcranial Cerebral Oximetry [ Time Frame: Monthly until MTD then every six months, up to ten years ]Non-invasive transcranial cerebral oximetry
- Splenic function [ Time Frame: Annually up to ten years ]Splenic function as measured by pocked red blood cell counts ("pit counts")
- Kidney function [ Time Frame: Annually, up to ten years ]Kidney function as measured by BUN/creatinine, urinalysis, and cystatin-C
- Cardiac function (assessment and growth) [ Time Frame: Every Five Years, up to 21 years of age ]Cardiac function as measured by echocardiogram and ECG
- Assessment of Growth [ Time Frame: Every six months, up to ten years ]Assessment of growth as defined by height and weight
To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.
Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT02286154
|Contact: Amanda Pfeiffer, LPC, CCRPfirstname.lastname@example.org|
|Contact: Adriane Hausfeld, RN,BSN,CCRP||(513)email@example.com|
|Principal Investigator:||Charles Quinn, MD, MS||Children's Hospital Medical Center, Cincinnati|