Assessment of the Efficacy of High-Dose Intravenous Vitamin C on Severity of Acute Graft Versus Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation: A Randomized, Triple-Blind, Placebo-Control Trial
Assessment of the Efficacy of High-Dose Vitamin C on Severity of Acute Graft Versus Host Disease After Allogeneic HSCT
Design
Prospective, Single-center, Triple-blind, Randomized, Placebo-Controlled Clinical Trial.
The Balance Blocked Randomization method with Stata software will be used for randomization. The study will be conducted on 260 patients hospitalized in the bone marrow transplant departments of Shariati Hospital. After the number of patients reaches 28, an interim analysis will be done and based on that, a decision will be made regarding the continuation of the study.
Settings and conduct
Candidates for allogeneic transplantation of Research Institute of Oncology, Hematology and Cell Therapy are divided into two groups receiving vitamin C and placebo according to the random block list. Data are obtained by researchers in the BMT ward, post-transplant clinic, and emergency through questionnaires.
Participants/Inclusion and exclusion criteria
Inclusion criteria: Allogeneic HSCT due to hematologic malignancies; Patient age ≥ 18; HLA-full-matched stem cell related donor; normal kidney and liver function
Exclusion criteria: Known allergy to vitamin C; G6PDH deficiency; History of kidney stones or oxaluria during the last 5 years; Patients with hemochromatosis; Inability to swallow oral medicine from the 15th day onwards; Known or suspected state of malabsorption or gastrointestinal obstruction
Intervention groups
Vitamin C or placebo (50 mg/kg/day) is administered intravenously to each participant in 3 divided doses from day +1 after transplantation to day +14. Participants will then take vitamin C or a placebo in the form of oral effervescent 500 mg tablets once a day for up to 100 days after the transplant.
Main outcome variables
Cumulative incidence and severity of acute GVHD during 100 days after HSCT
General information
Reason for update
Acronym
VitCHSCT
IRCT registration information
IRCT registration number:IRCT20140818018842N31
Registration date:2023-02-27, 1401/12/08
Registration timing:registered_while_recruiting
Last update:2023-02-27, 1401/12/08
Update count:0
Registration date
2023-02-27, 1401/12/08
Registrant information
Name
Leyla Sharifi Aliabadi
Name of organization / entity
Research Institute for Hematology, Oncology and Stem Cell Transplantation,Tehran University of Medic
Country
Iran (Islamic Republic of)
Phone
+98 21 8490 2635
Email address
ctu@sina.tums.ac.ir
Recruitment status
Recruitment complete
Funding source
Expected recruitment start date
2023-02-19, 1401/11/30
Expected recruitment end date
2023-09-21, 1402/06/30
Actual recruitment start date
empty
Actual recruitment end date
empty
Trial completion date
empty
Scientific title
Assessment of the Efficacy of High-Dose Intravenous Vitamin C on Severity of Acute Graft Versus Host Disease After Allogeneic Hematopoietic Stem Cell Transplantation: A Randomized, Triple-Blind, Placebo-Control Trial
Public title
Vitamin C in Allogeneic Hematopoietic Stem Cell Transplantation
Purpose
Prevention
Inclusion/Exclusion criteria
Inclusion criteria:
Allogeneic hematopoietic stem cells transplantation due to any of the following hematological malignancies: Acute lymphoblastic leukemia (ALL)/ Acute myelogenous leukemia (AML)/ Myelodysplasia (MDS)/ Hodgkin's lymphoma (HL)/ non-Hodgkin's lymphoma (NHL)
Patient age ≥ 18
Patients must also receive a full myeloablative conditioning regimen
HLA-full-matched stem cell donor, either related or unrelated from peripheral blood stem cell or bone marrow
Estimated creatinine clearance ≥60 ml/min
Serum total bilirubin ≤ 2 x upper limit of normal value (ULN) and AST and ALT ≤ 2 x ULN
Karnofsky Performance Status of 60-100% or Eastern Cooperative Oncology Group (ECOG) performance status ≤2
Ability to understand and the willingness to sign a written informed consent document
Exclusion criteria:
Known allergy to vitamin C
G6PDH deficiency
Patients with hemochromatosis
History of kidney stones or oxaluria during the last 5 years
Uncontrolled viral, fungal, or bacterial infection
Allogeneic or autologous hematopoietic stem cells transplantation in the past 12 monthsPregnancy or breastfeeding
Left ventricular ejection fraction < 40%
Patient participation in another similar research project simultaneously
Pregnancy or breastfeeding
Age
From 18 years old
Gender
Both
Phase
2-3
Groups that have been masked
Participant
Care provider
Investigator
Outcome assessor
Data analyser
Sample size
Target sample size:
260
Randomization (investigator's opinion)
Randomized
Randomization description
For randomization, the Balance Blocked Randomization method will be used Stata software. Random allocation will be done using blocks of sizes 6 and 8. The total sample size will be estimated as 260 patients. In this way, random samples will be determined using the ralloc module (Random allocation of treatments in controlled trials) in Stata software.
Blinding (investigator's opinion)
Triple blinded
Blinding description
Regarding the preparation of placebo:
Injectable form: the treatment group will receive daily vitamin C in 5% dextrose and the control group will receive an equivalent volume of distilled water in 5% dextrose instead of vitamin C. Due to the blinding of the nursing staff, the preparation of the above solutions will be done by the pharmacist, who is not involved in the research but has the randomization list, in the clean room of the pharmacy of Shariati Hospital.
Oral form: It is in the form of effervescent tablets of 500 mg, which drug and placebo with a completely similar appearance are prepared by a pharmaceutical company.
The randomization sequence is prepared by a statistician who has no connection with the patients. The researchers and participants will be unaware of the study sequence. After confirming the entry of a new patient into the study and registering the patient's code, the coordinator who is stationed at the patient registration site places the patient in the treatment groups based on the specified randomization sequence.
Placebo
Used
Assignment
Parallel
Other design features
Since patient safety is the priority of this research, after the number of patients reaches 28, an interim analysis will be performed and a decision will be made regarding the continuation of the study.
Secondary Ids
empty
Ethics committees
1
Ethics committee
Name of ethics committee
The Institute of Pharmaceutical Sciences -Tehran University of Medical Sciences
Street address
Poursina St., Tehran University of Medical Sciences, Faculty Pharmacy, Institute of Pharmaceutical Sciences (TIPS)
Patients will be monitored for acute GVHD at least daily until discharge and then at each outpatient visit until day 100+. The nature and extent of skin involvement will be determined by examination. Staging will be also based on the extent and type of skin involvement. Gastrointestinal GVHD requires 24-hour stool volume for staging. In addition, a history will be taken to document the presence or absence of abdominal pain, nausea, and vomiting. Patients will also be examined for the presence of ileus. The staging of liver involvement is also determined by the increase in total serum bilirubin. The grade of acute GVHD used to evaluate treatment will be the highest grade developed during the entire evaluation period.
Secondary outcomes
1
Description
Time from transplant to neutrophil engraftment
Timepoint
0 - 30 Days after HSCT
Method of measurement
Daily CBC or bone marrow aspiration and biopsy if needed
2
Description
Time from transplant to platelet engraftment
Timepoint
0 - 30 Days after HSCT
Method of measurement
Daily CBC or bone marrow aspiration and biopsy if needed
3
Description
Cumulative incidence, severity and duration of oral mucositis
Timepoint
0 - 100 days after HSCT
Method of measurement
Clinical assessment, oral and pharyngeal mucositis is evaluated clinically and based on CTCAE v5.0 daily until discharge or recovery and then at every outpatient visit to the clinic until day 100+.
4
Description
Safety and tolerability of the vitamin C regimen
Timepoint
0 - 100 days after HSCT
Method of measurement
Clinical assessment, Vitamin C adverse events (AEs) reported using criteria in the CTCAE v5.0
5
Description
Ascorbic acid plasma levels in patients receiving MAC regimen
Timepoint
0 - 30 days after HSCT
Method of measurement
With High-performance liquid chromatography (HPLC) method
6
Description
Relapse rates
Timepoint
At least 100 days after HSCT
Method of measurement
Bone marrow aspiration and biopsy.
7
Description
Overall survival
Timepoint
At least 100 days after HSCT
Method of measurement
Patient follow-up
Intervention groups
1
Description
Intervention group: IV vitamin C 50 mg/kg/day divided in 3 doses beginning on posttransplant; Day +1 and continuing through Day +14 Each dose of 1 g given in 100 mL of 5% dextrose/water over 30 minutes (33 mg/min) every 8 hours.After completion of the IV vitamin C doses, oral vitamin C 500 mg daily beginning on Day +15 and continuing until Day +100
Category
Treatment - Drugs
2
Description
Control group: Placebo IV Day +1 to +14, followed with oral, one placebo tablet daily beginning on Day +15 and continuing until Day +100.
Category
Placebo
Recruitment centers
1
Recruitment center
Name of recruitment center
Research Institute of Oncology, Hematology, and Cell Therapy