Thalassemia, BetaPhase 2NCT03183375
The Efficacy and Safety of HYDROXYUREA in Management of Beta Thalassemia Patients in Karachi Pakistan
A Phase 2 study testing Hydroxyurea in people with Thalassemia, Beta, run by Dr.Saqib Hussain Ansari at 1 site in Pakistan.
Trial summary
Objectives Primary objectives: To determine the efficacy of Hydroxyurea in the study participants. Hypothesis: The study will result in either maintenance or rise in hemoglobin as compared to the control treatment. Secondary objectives: To determine the compliance of Hydroxyurea in study participants. Read more about this study
- Who is it for?
- Ages 6 months and older
- Conditions the study is for
- Thalassemia, Beta
- What is being tested?
- Hydroxyurea
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 100 participants
- Where
- 1 sitePakistan
- Study dates
- 21 Aug 2017to 30 Jun 2018
- Phase
- Phase 2
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 6 months and older
- All sexes
- No healthy volunteers
- Child, Adult, Older adult
Who may be able to join
- Patients with homozygous beta thalassemia major diagnosed on the basis of genetic mutation
- Beta thalassemia intermedia (patients carrying homozygous, heterozygous or compound heterozygous beta thalassemia genes) (HbS, HbE)
- Those patients who do not have baseline HbE suggestive of beta thalassemia, genetic mutations will be performed to confirm the diagnosis.
- Age: 6 months and onwards
- Gender: Either
- Able to understand study procedures and to comply with them for the entire length of the study.
- Provide written informed consent if aged 18 years and above and if minor that is below 18 years (Parental consent will be taken)
Who cannot join
- Chronic liver disease, renal failure, history of stroke
- Participants who have developed immune hemolytic anemia
- Spleenomegaly (liver and spleen >5 cm below coastal margin
- If allergic or sensitive to Hydroxyurea or its ingredients
- Patients on immunosuppressants including Azathiopine or any other drug causing bone marrow suppression, Hepatitis C treatment that may cause red cell suppression and NSAIDS
- Inability or unwillingness of individual or legal guardian/representative to give written informed consent.
Trial locations and contacts
1 site in 1 country.
Pakistan1 site, 1 recruiting
- Recruiting
Omair Sana Foundation
Karachi, Sindh, 75300
Saqib H Ansari, MBBS, DCH, DPGN, Mphil, PhD, 03002118018, muddasirsaqib@yahoo.com
Salima M Ali, BScN, MS, 03322696554, sohanisalima@gmail.com
About this study
Official title: An Open Label Randomized Controlled Trial to Evaluate the Efficacy and Safety of HYDROXYUREA in Management of Beta Thalassemia Patients in Karachi Pakistan
Objectives
Primary objectives:
Read more
- To determine the efficacy of Hydroxyurea in the study participants.
- Hypothesis: The study will result in either maintenance or rise in hemoglobin as compared to the control treatment.
Secondary objectives:
- To determine the compliance of Hydroxyurea in study participants.
- To determine the safety of Hydroxyurea in the study participants. Design and Outcomes
An open label randomized controlled trial to test the efficacy and safety of Hydroxyurea on beta thalassemia major patients. It is a six months study. Findings of physical examination, vital sign variables, laboratory variables and ultrasound at baseline, during and end of the study will be listed. Schedule of intervention is mentioned in section 6.1. later in the protocol.
Interventions and Duration Hydroxyurea will be given to the participants in intervention arm along with the standard treatment if thalassemia (blood transfusion and iron chelation therapy) and the control arm will receive the standard treatment (blood transfusion and iron chelation therapy) only. Each participant will be followed up for 6 months after initiating the intervention. Intervention will be given for 6 months or until the participant withdraws from the study or due to any reason, the investigator stops the intervention.
Sample Size and Population This pilot study will be done on 100 patients initially. Stratified randomization will be done on the basis of presence of Xmn polymorphism. And the study population will be assigned to intervention or control arm randomly through a computer software (randomizer.org).
Read the detailed description
Study Enrollment Procedures
- The study participants will be examined on the screening visit to assess their eligibility to participate. Each participant will consent in writing (Appendix I) to the screening process before the start of the examination and laboratory or radiology investigations. Screening log will be maintained to record this information.
- Parental consent (for minors age group < 18 years) will be obtained from a legal guardian accompanying the participant.
- The research unit will produce a computer generated sets of random allocations stratified on the basis of presence or absence of Xmn in advance of the start of the study. They will be then sealed in consecutively numbered opaque envelopes. The study participants will be randomly assigned to the investigation arm or control arm accordingly.
Storage and Accountability
All study drugs must be kept in a secure place under adequate storage conditions - protected from moisture and light and under required temperature (in refrigerator if required). Records of dispensing and returns will be maintained by the trial site (Omair Sana Foundation) in form of counts of tablets dispensed or returned. The subject must return all unused study medication for each treatment period to the trial center.
Statistical Analysis plan Intention to treat analysis Each participant will be analyzed in the group he was assigned to (investigational arm and control arm) at the time of study initiation rather than what he /she will take (drug orstandard treatment). Data will be entered and analyzed through statistical software SPSS version 17. Descriptive and inferential statistics will be analyzed. Descriptive statistics will be presented as means, standard deviations and ninety five percent confidence levels of the means for continuous variables and frequency and percentages for categorical variable.
Analysis per protocol patient:
Additional sensitivity analysis will be done as per protocol patient. Those participants will be analyzed who will receive at least 80% of the assigned intervention.
Inferential analysis: The mean difference in the efficacy and safety parameters from baseline to end will be reported along with p-value and ninety five percent confidence intervals. To find the difference, dependent T-test will be performed in case of normally distributed variables, Wilcoxan Signed Rank test for variables assuming non-parametric distribution and chi-square test of independence will be performed in case of categorical variables. The results will be displayed in form of graphs and tables. The results will be considered as statistically significant if p-value is less than 0.05 (level of significance).
Baseline characteristics: The demographic, background and baseline data and baseline characteristics of study participants will be presented descriptively. Protocol violations will be listed per participant, describing the nature of the violation. Participants failing to complete the study (as well as the times and reasons for discontinuation) will be displayed.
Analysis of Safety: Adverse Events, as reported throughout the course of the trial will be listed. Pre-, study and post-study findings of physical examination, vital sign variables, laboratory variables will be listed individually and summarized; values outside the normal range will be highlighted.
DATA COLLECTION AND QUALITY ASSURANCE Data Collection Forms Standard CRF (Appendix II) is designed for the data collection purpose. Data Management Database will be formed in order to record data from the folders for the trial patients.
Quality Assurance Data from the study will be collected in CRFs. Data editing will be performed at the trial center, comparing source and CRF entries.
During the study an independent monitor will visit the investigational site randomly without prior notification to confirm that the facilities remain acceptable, that the investigational team is adhering to the protocol and that data are being accurately recorded in the CRFs. Source data verification (a comparison of the data in the CRF with the participants' laboratory test results and other source documents) will also be performed.
Authorized representatives of the regulatory authority (e.g. IRB) may visit the center to perform inspections, including source data verification.
Clean File for the final database will be declared when all data have been entered and a quality check on a sample of the data has been performed. The database will be locked after Clean File has been declared and data extracted for statistical analysis.
Study committee meetings will be held as needed prior to or during the study. The medical, nursing and other research staff involved in the study will receive proper training on how to conduct the study and record the information according to the protocol.
- Conditions
- Thalassemia, Beta
- Being tested
- Hydroxyurea
- Medical subject headings
- beta-Thalassemia
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
HydroxyureaDrug
Hydroxyurea (starting from 10mg/kg/day with increasing dose by 2mg/kg/day until the desired response is achieved. The maximum dose given will be 20mg/kg/day)
| Study group | Role | What they receive |
|---|---|---|
| Hydroxyurea arm | Experimental | This arm will be given investigational drug that is Hydroxyurea .This intervention will be given along with the standard treatment that is blood transfusion and iron chelation. Receives: Drug: Hydroxyurea |
| Standard arm | No intervention | this arm will only receive the standard treatment which is blood transfusion and iron chelation |
What is being measured
The primary outcome is the main question the study is designed to answer.
No. of participants who become responders or partial responders
The responders will be those who become transfusion independent (in those who were transfusion dependent before Hydroxyurea) or those who maintain or show 1-2 g/dl increase in Hb from baseline and partial responders will be those whose transfusion requirement decreases by atleast 50% as compared to baseline.
Measured: 6 months
Secondary outcomes (3)
The compliance of Hydroxyurea in study participants.
Compliance will be defined as actual number of tablets used/taken divided by the estimated number of tablets to be used/taken.
Measured: 6 months
Number of participants with abnormal/deranged laboratory values
Participants with at least 1 of the following deranged laboratory values:
- Deranged renal function (creatinine >2, Urea above normal range),
- Liver function (SGPT 100 times more from baseline)
- Neutropenia (neutrophil <1000)
- Platelets < 50, 000
- Deranged renal function (creatinine >2, Urea above normal range),
- Liver function (SGPT 100 times more from baseline)
- Neutropenia (neutrophil <1000)
- Platelets < 50, 000 Deranged renal function (creatinine >2, Urea above normal range), Liver function (SGPT 100 times more from baseline),Neutropenia (neutrophil <1000),Platelets < 50, 000
Measured: 6 months
No. of participants with severe adverse events related to the intervention
Measured: 6 months
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted12 Jun 2017
- Study start21 Aug 2017
- Primary completion30 Apr 2018 (estimated)
- Study completion30 Jun 2018 (estimated)
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Other trials for Thalassemia, BetaStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase 2
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Model description
- One is intervention arm which will be given investigational drug along with standard treatment and one will be control arm which will be given standard treatment only. Both groups will be assigned to only one treatment parallelly.
- Masking
- None (open label)
- Enrolment
- 100 participants (estimated)
Sponsor and investigators
- Lead sponsor
- Dr.Saqib Hussain Ansari
- Sponsor type
- University, hospital or other
- Responsible party
- Sponsor-investigator, Dr.Saqib Hussain Ansari, Omair Sana Foundation
- Investigators
- Saqib H Ansari, MBBS, DCH, DPGN, Mphil, PhD, Principal investigator, Omair Sana Foundation
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT03183375
- Sponsor's protocol ID
- ERB0002
- Status last verified
- Sep 2017
- First submitted
- 5 Jun 2017
- Last updated
- 20 Sep 2017
- Results posted
- No
- Data monitoring committee
- Yes
- FDA-regulated drug
- No
- FDA-regulated device
- No
- Individual data sharing
- No
Study at a glance
From the registry record, last updated by the sponsor on 20 Sep 2017. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- An Open Label Randomized Controlled Trial to Evaluate the Efficacy and Safety of HYDROXYUREA in Management of Beta Thalassemia Patients in Karachi Pakistan
- ClinicalTrials.gov ID
- NCT03183375
- Acronym / sponsor ID
- ERB0002
- Conditions
- Thalassemia, Beta
- Phase
- Phase 2
- Study type
- Interventional
- Recruitment status
- Unknown status
- Enrolment
- 100 participants (estimated)
- Lead sponsor
- Dr.Saqib Hussain AnsariUniversity, hospital or other
- Study start
- 21 Aug 2017 (actual)
- Primary completion
- 30 Apr 2018 (estimated)
- Study completion
- 30 Jun 2018 (estimated)
- First posted
- 12 Jun 2017 (actual)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
Objectives
Primary objectives:
- To determine the efficacy of Hydroxyurea in the study participants.
- Hypothesis: The study will result in either maintenance or rise in hemoglobin as compared to the control treatment.
Secondary objectives:
- To determine the compliance of Hydroxyurea in study participants.
- To determine the safety of Hydroxyurea in the study participants. Design and Outcomes
An open label randomized controlled trial to test the efficacy and safety of Hydroxyurea on beta thalassemia major patients. It is a six months study. Findings of physical examination, vital sign variables, laboratory variables and ultrasound at baseline, during and end of the study will be listed. Schedule of intervention is mentioned in section 6.1. later in the protocol.
Interventions and Duration Hydroxyurea will be given to the participants in intervention arm along with the standard treatment if thalassemia (blood transfusion and iron chelation therapy) and the control arm will receive the standard treatment (blood transfusion and iron chelation therapy) only. Each participant will be followed up for 6 months after initiating the intervention. Intervention will be given for 6 months or until the participant withdraws from the study or due to any reason, the investigator stops the intervention.
Sample Size and Population This pilot study will be done on 100 patients initially. Stratified randomization will be done on the basis of presence of Xmn polymorphism. And the study population will be assigned to intervention or control arm randomly through a computer software (randomizer.org).
Detailed description
Study Enrollment Procedures
- The study participants will be examined on the screening visit to assess their eligibility to participate. Each participant will consent in writing (Appendix I) to the screening process before the start of the examination and laboratory or radiology investigations. Screening log will be maintained to record this information.
- Parental consent (for minors age group < 18 years) will be obtained from a legal guardian accompanying the participant.
- The research unit will produce a computer generated sets of random allocations stratified on the basis of presence or absence of Xmn in advance of the start of the study. They will be then sealed in consecutively numbered opaque envelopes. The study participants will be randomly assigned to the investigation arm or control arm accordingly.
Storage and Accountability
All study drugs must be kept in a secure place under adequate storage conditions - protected from moisture and light and under required temperature (in refrigerator if required). Records of dispensing and returns will be maintained by the trial site (Omair Sana Foundation) in form of counts of tablets dispensed or returned. The subject must return all unused study medication for each treatment period to the trial center.
Statistical Analysis plan Intention to treat analysis Each participant will be analyzed in the group he was assigned to (investigational arm and control arm) at the time of study initiation rather than what he /she will take (drug orstandard treatment). Data will be entered and analyzed through statistical software SPSS version 17. Descriptive and inferential statistics will be analyzed. Descriptive statistics will be presented as means, standard deviations and ninety five percent confidence levels of the means for continuous variables and frequency and percentages for categorical variable.
Analysis per protocol patient:
Additional sensitivity analysis will be done as per protocol patient. Those participants will be analyzed who will receive at least 80% of the assigned intervention.
Inferential analysis: The mean difference in the efficacy and safety parameters from baseline to end will be reported along with p-value and ninety five percent confidence intervals. To find the difference, dependent T-test will be performed in case of normally distributed variables, Wilcoxan Signed Rank test for variables assuming non-parametric distribution and chi-square test of independence will be performed in case of categorical variables. The results will be displayed in form of graphs and tables. The results will be considered as statistically significant if p-value is less than 0.05 (level of significance).
Baseline characteristics: The demographic, background and baseline data and baseline characteristics of study participants will be presented descriptively. Protocol violations will be listed per participant, describing the nature of the violation. Participants failing to complete the study (as well as the times and reasons for discontinuation) will be displayed.
Analysis of Safety: Adverse Events, as reported throughout the course of the trial will be listed. Pre-, study and post-study findings of physical examination, vital sign variables, laboratory variables will be listed individually and summarized; values outside the normal range will be highlighted.
DATA COLLECTION AND QUALITY ASSURANCE Data Collection Forms Standard CRF (Appendix II) is designed for the data collection purpose. Data Management Database will be formed in order to record data from the folders for the trial patients.
Quality Assurance Data from the study will be collected in CRFs. Data editing will be performed at the trial center, comparing source and CRF entries.
During the study an independent monitor will visit the investigational site randomly without prior notification to confirm that the facilities remain acceptable, that the investigational team is adhering to the protocol and that data are being accurately recorded in the CRFs. Source data verification (a comparison of the data in the CRF with the participants' laboratory test results and other source documents) will also be performed.
Authorized representatives of the regulatory authority (e.g. IRB) may visit the center to perform inspections, including source data verification.
Clean File for the final database will be declared when all data have been entered and a quality check on a sample of the data has been performed. The database will be locked after Clean File has been declared and data extracted for statistical analysis.
Study committee meetings will be held as needed prior to or during the study. The medical, nursing and other research staff involved in the study will receive proper training on how to conduct the study and record the information according to the protocol.
Study design
- Primary purpose
- Treatment
- Allocation
- Randomised
- Intervention model
- Parallel groups
- Masking
- None (open label)
- Number of arms
- 2
- Model description
- One is intervention arm which will be given investigational drug along with standard treatment and one will be control arm which will be given standard treatment only. Both groups will be assigned to only one treatment parallelly.
| Arm | Type | Receives |
|---|---|---|
| Hydroxyurea arm | Experimental | Drug: HydroxyureaThis arm will be given investigational drug that is Hydroxyurea .This intervention will be given along with the standard treatment that is blood transfusion and iron chelation. |
| Standard arm | No intervention | –this arm will only receive the standard treatment which is blood transfusion and iron chelation |
Who may qualify
- Ages
- 6 months and older
- Sex
- All
- Healthy volunteers
- Not accepted
- Age groups
- Child, Adult, Older adult
Key inclusion criteria (7 listed)
- Patients with homozygous beta thalassemia major diagnosed on the basis of genetic mutation
- Beta thalassemia intermedia (patients carrying homozygous, heterozygous or compound heterozygous beta thalassemia genes) (HbS, HbE)
- Those patients who do not have baseline HbE suggestive of beta thalassemia, genetic mutations will be performed to confirm the diagnosis.
- Age: 6 months and onwards
- Gender: Either
Key exclusion criteria (6 listed)
- Chronic liver disease, renal failure, history of stroke
- Participants who have developed immune hemolytic anemia
- Spleenomegaly (liver and spleen >5 cm below coastal margin
- If allergic or sensitive to Hydroxyurea or its ingredients
- Patients on immunosuppressants including Azathiopine or any other drug causing bone marrow suppression, Hepatitis C treatment that may cause red cell suppression and NSAIDS
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| HydroxyureaHydroxyurea (starting from 10mg/kg/day with increasing dose by 2mg/kg/day until the desired response is achieved. The maximum dose given will be 20mg/kg/day) | Drug | Hydroxyurea arm |
Primary outcome
No. of participants who become responders or partial responders
Time frame: 6 months
The responders will be those who become transfusion independent (in those who were transfusion dependent before Hydroxyurea) or those who maintain or show 1-2 g/dl increase in Hb from baseline and partial responders will be those whose transfusion requirement decreases by atleast 50% as compared to baseline.
3 secondary outcomes
The compliance of Hydroxyurea in study participants.
Time frame: 6 months
Number of participants with abnormal/deranged laboratory values
Time frame: 6 months
No. of participants with severe adverse events related to the intervention
Time frame: 6 months
Results and safety
Results are not available in the source record.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 20 Sep 2017.
- Individual participant dataSharing planned: No
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Saqib H Ansari, MBBS, DCH, DPGN, Mphil, PhD principal investigator
Omair Sana Foundation
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A Phase 2 study testing Hydroxyurea in people with Thalassemia, Beta, run by Dr.Saqib Hussain Ansari at 1 site in Pakistan.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 7 inclusion and 6 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: status not confirmed, as of the sponsor's last update on 20 Sep 2017. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in Pakistan. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
What does this phase mean?
Phase 2 studies give the treatment to a larger group to see whether it has the intended effect and to keep checking safety.
Not every study follows the same path, and some studies (observational studies, device studies) have no phase.
Are results available for this study?
Results are not available in the source record.
How can a doctor refer a patient or contact the research team?
Contact Saqib H Ansari, MBBS, DCH, DPGN, Mphil, PhD (+93002118018, muddasirsaqib@yahoo.com), or a site near the patient. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
No. of participants who become responders or partial responders (time frame: 6 months). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 20 Sep 2017.