Efficacy of combination therapy of L-glutamine and Hydroxyurea in comparison with Hydroxyurea alone in patients with sickle cell anemia: a randomized, double-blinded clinical trial
Comparison of combination therapy of L-glutamine and hydroxyurea compared with hydroxyurea alone in patients with sickle cell anemia
Design
The final sample size is 126 people in total (63 people in each group)
This study is a randomized, controlled, parallel clinical trial in which all patients are examined in two groups. Intervention group A will receive L-glutamine and hydroxyurea combination therapy, and group B will receive hydroxyurea treatment alone (control group).
Settings and conduct
This study is a randomized, controlled trial (standard treatment of hydroxyurea), double-blind and 6-month parallel group.
The allocation of two randomized block blinds is encoded in numbered envelopes and is prepared according to the sample size and will be provided to the patient's attending physician.
Participants/Inclusion and exclusion criteria
Patients who are at least 5 years old; diagnosed with sickle cell anemia, and have documented at least two pain crises in the past year are eligible to enter the study. Patients who receive hydroxyurea treatment at a dose that is constant for at least 3 months prior to screening and intend to continue that treatment are eligible to participate. Exclusion criteria are: Patients admitted for non-sickle cell disease within 2 months prior to screening, normalized international prothrombin time ratio greater than 2.0, serum albumin level less than 3.0 g / dL, Each blood product is taken 3 weeks before screening and has clinically significant kidney or liver disease, treated with L-glutamine within 30 days before screening.
Intervention groups
Receive a combination of L-glutamine and hydroxyurea
Main outcome variables
The main outcome variable of the study is the number of pain crises at the end of 6 months.
General information
Reason for update
Acronym
IRCT registration information
IRCT registration number:IRCT20210715051904N1
Registration date:2022-02-19, 1400/11/30
Registration timing:registered_while_recruiting
Last update:2022-02-19, 1400/11/30
Update count:1
Registration date
2022-02-19, 1400/11/30
Registrant information
Name
Nader Shakibazad
Name of organization / entity
Country
Iran (Islamic Republic of)
Phone
+98 77 3335 1048
Email address
shakibn@bpums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2022-02-14, 1400/11/25
Expected recruitment end date
2022-10-17, 1401/07/25
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Efficacy of combination therapy of L-glutamine and Hydroxyurea in comparison with Hydroxyurea alone in patients with sickle cell anemia: a randomized, double-blinded clinical trial
Public title
The effect of combination therapy of L-glutamine and hydroxyurea in patients with sickle cell anemia
Purpose
Treatment
Inclusion/Exclusion criteria
Inclusion criteria:
Patients with sickle-cell syndrome
Age more than five-year-old
No other accompanying hematologic diseases
All patients should be on Hydroxyurea
At least two (extreme) pain crises have been documented in the past year (defining a pain crisis as pain that results from treatment with a drug or injectable ketorolac in the emergency department (ED) (or outpatient treatment center) or during hospitalization. Becomes)
Exclusion criteria:
Occurrence of life-threatening events not related to SCD during treatment
Patient dissatisfaction with participation in the study
Serum albumin levels are less than 3 g / dL
Internationally normalized ratios of prothrombin time are higher than 2.0
The treated with L-glutamine within 30 days prior to screening.
Age
From 5 years old
Gender
Both
Phase
3
Groups that have been masked
Participant
Care provider
Investigator
Outcome assessor
Data analyser
Sample size
Target sample size:
126
Randomization (investigator's opinion)
Randomized
Randomization description
This study is a randomized controlled clinical trial in which all patients are examined in two groups, which we represent with two symbols A and B. Group A will receive L-glutamine and hydroxyurea combination therapy in the intervention (intervention group) and group B will receive hydroxyurea treatment alone (control group). Participants in the study will be randomly divided into two groups A and B equal to .... individual. In order to randomly assign individuals to two equal groups to receive the intervention, the Permuted Block Randomization method with a block size of 6 has been used. The block randomization scheme was created using the free Randomization.com website (http://randomization.com). From the order of the Permuted Block Randomization table, the allocator and evaluator should not be aware of the type of intervention being performed on the individual and the size of the block. Thus, it can be said that the data allocation will remain hidden until the end of the study. Thus, each participant will be assigned to intervention or control groups and will enter the study.
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Blinding (investigator's opinion)
Double blinded
Blinding description
From the order of the Permuted Block Randomizotion table, the allocator and evaluator should not be aware of the type of intervention being performed on the individual and the size of the block. Thus, it can be said that the data allocation will remain hidden until the end of the study. In this way, each participant will be assigned to intervention or control groups and will be included in the study. Pain Crisis Judgment and Laboratory Tests: All pain crises reported in the case report forms will be recorded by the researchers. An independent judging panel consisting of two hematologists-oncologists who are unaware of the assignment of the trial team will evaluate each episode to determine whether the event meets the definition of a pain crisis for performance evaluation.
Placebo
Used
Assignment
Parallel
Other design features
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
Research Ethics Committees of Bushehr province university of medical sciences
Street address
BPUMS Vice chancellery for Education, Bushehr University of Medical Sciences, Salman Farsi St, Alamdar St, Bushehr, Iran.
Sickle-cell disorders, Sickle-cell anaemia with crisis, Sickle-cell anaemia without crisis, Double heterozygous sickling disorders, Sickle-cell trait, Other sickle-cell disorders
Primary outcomes
1
Description
Number of pain crisis
Timepoint
Before intervention and 6 months after intervention
Method of measurement
Clinical examination by a pediatric hematologist and oncologist
2
Description
Number of hospitalizations for pain associated with sickle cell anemia
Timepoint
Before intervention and 6 months after intervention
Method of measurement
Clinical examination by a pediatric hematologist and oncologist
Secondary outcomes
1
Description
Number of Priapism event
Timepoint
Before intervention and 6 months after intervention
Method of measurement
Clinical examination by a pediatric hematologist and oncologist
2
Description
Number of acute chest syndrome
Timepoint
Before intervention and 6 months after intervention
Method of measurement
Clinical examination by a pediatric hematologist and oncologist
3
Description
Number of splenic sequestration events
Timepoint
Before intervention and 6 months after intervention
Method of measurement
Clinical examination by a pediatric hematologist and oncologist
Intervention groups
1
Description
Intervention group: Intervention group: The allocation of two randomized block blinds is encoded in numbered envelopes and is prepared according to the number of samples and will be provided to the patient's attending physician. Therefore, eligible patients will be randomly divided into a 1: 1 ratio for L-glutamine and hydroxyurea combination therapy or hydroxyurea alone, with randomized block allocation. The planned treatment period will be 6 months, during which patients, in addition to consuming hydroxyurea, take L-glutamine powder orally twice a day at a dose of approximately 0.3 g / kg body weight per dose (10 g, 20 g). Grams or 30 grams [maximum dose] per day). The contents of the package will be mixed with an unheated drink or food and consumed immediately. Patients will be contacted by telephone each week between monthly visits to encourage adherence. The validity of the test group assignment and the correct supply of L-glutamine or placebo for each patient will be verified by an independent research drug service. Patients can receive blood transfusions and other necessary clinical treatments if needed.
Category
Treatment - Drugs
2
Description
Control group: The allocation of two randomized block blinds is encoded in numbered envelopes and is prepared according to the number of samples and will be provided to the patient's attending physician. Therefore, eligible patients will be randomly divided into a 1: 1 ratio for L-glutamine and hydroxyurea combination therapy or hydroxyurea alone, with randomized block allocation. The planned treatment period will be 6 months, during which the control group will receive placebo powder (100% maltodextrin) orally twice a day. Experimental drug and placebo in individual packages and visually identical contain 5 grams of white powder without taste is provided, and all packages will be returned by patients to assess compliance. The contents of the package will be mixed with an unheated drink or food and consumed immediately. Patients will be contacted by telephone each week between monthly visits to encourage adherence. The validity of the test group assignment and the correct supply of L-glutamine or placebo for each patient will be verified by an independent research drug service. Patients can receive blood transfusions and other necessary clinical treatments if needed.