Home » Trials » SLCTR/2018/024


Efficacy and safety of oral hydroxyurea in transfusion dependent beta-thalassaemia: a randomized double-blind placebo-controlled clinical trial

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SLCTR Registration Number

SLCTR/2018/024


Date of Registration

01 Aug 2018

The date of last modification

Jan 28, 2019



Application Summary


Scientific Title of Trial

Efficacy and safety of oral hydroxyurea in transfusion dependent beta-thalassaemia: a randomized double-blind placebo-controlled clinical trial


Public Title of Trial

Effectiveness of hydroxyurea treatment compared to placebo in reducing transfusions in beta-thalassaemia patients.


Disease or Health Condition(s) Studied

Beta-thalassaemia


Scientific Acronym

None


Public Acronym

None


Brief title

None


Universal Trial Number

U1111-1214-3595


Any other number(s) assigned to the trial and issuing authority

Ref. No: P/116/05/2018 -Ethics review committee, Faculty of Medicine, University of Kelaniya


Trial Details


What is the research question being addressed?

Is hydroxyurea safe and effective in reducing transfusion requirement in patients with transfusion dependent beta-thalassaemia?


Type of study

Interventional


Study design

Allocation

Randomized controlled trial


Masking

Double blinded


Control

Placebo


Assignment

Parallel


Purpose

Treatment


Study Phase

Phase 2-3


Intervention(s) planned

Place of study will be Adolescent and Adult Thalassaemia Center of the Colombo North Teaching Hospital, Ragama, Sri Lanka.

Method of randomization will be simple randomization using an online simple randomization tool. Subjects will be randomized to two arms

Active arm treated with hydroxyurea

Control arm treated with placebo (This is a matching capsule which contains ingredients identical to hydroxyurea except for the active ingredient).

Investigational product [Active hydroxyurea] will be administered at a dose of 500mg (if body weight =<50kg) or 1000mg (if body weight >50kg) orally by subject once daily for six months. Placebo will also be administered once daily for six months.

The following will be blinded; participants, data collectors, outcome adjudicators and data analysts


Inclusion criteria

  1. Male and female patients with confirmed genotype of homozygous or compound heterozygous beta-thalassaemia major or HbE beta-thalassaemia
  2. Age above 12 years
  3. Patients who required more than 10 transfusions during the preceding year

Exclusion criteria

  1. Patients who have undergone bone marrow transplantation
  2. Patients with very high serum ferritin (>5000ng/ml)
  3. Sickle beta-thalassaemia
  4. Chronic liver disease
  5. Chronic kidney disease
  6. Patients with contraindications for hydroxyurea therapy (eg: hypersensitivity, severe anaemia with haemoglobin less than 5g/dl at the beginning of treatment, bone marrow depression, pregnancy and lactation)
  7. Patients who are expecting to get pregnant during next 12 months
  8. White blood cell count less than 4000/uL.
  9. Platelet count less than 150,000/uL.
  10. Evidence of active viral infection, including viral hepatitis
  11. Patients on immunosuppressant therapy


Primary outcome(s)

  1. Response to treatment: Complete response to treatment is defined as complete cessation of blood transfusions with a baseline haemoglobin >9.0g/dl during the treatment period. Partial response is defined as over 50% reduction in transfusion requirement during treatment period (=<3 transfusions during treatment 6 months) with baseline haemoglobin >7.0g/dl.

    Subjects will be evaluated monthly during the period of treatment by full blood count measurements.

    [

    At the end of six months of initiating treatment.

    ]

Secondary outcome(s)

  1. Compliance to hydroxyurea treatment (measured as actual number of tablets taken divided by the estimated number of tablets to be taken).

    [

    Compliance to hydroxyurea treatment will be assessed monthly for 6 months after initiating treatment

    ]
  2. Side effects of hydroxyurea

    Subjects will be evaluated monthly during the period of treatment. Evaluation includes an interview and physical examination by a trained medical officer to assess adverse effects of hydroxyurea. Following investigations will also be done to assess side effects of hydroxyurea; full blood count, serum creatinine and liver transaminases.

    [

    Side effects will be assessed monthly for 12 months after initiating treatment

    ]

Target number/sample size

90 (45 in each arm)


Countries of recruitment

Sri Lanka


Anticipated start date

2018-09-01


Anticipated end date

2020-02-28


Date of first enrollment


Date of study completion


Recruitment status

Pending


Funding source

National Research Council- Sri Lanka. Investigator Driven Grant # 18-030


Regulatory approvals

Not applicable



State of Ethics Review Approval


Status

Approved


Date of Approval

2018-06-26


Approval number

P/116/05/2018


Details of Ethics Review Committee

Name: Ethics Review Committee, Faculty of Medicine, University of Kelaniya
Institutional Address: PO Box 6, Thalagolla Road, Ragama Sri Lanka
Telephone: +94-11-2961267
Email: erckelaniya@gmail.com


Contact & Sponsor Information


Contact person for Scientific Queries/Principal Investigator

Dr Sachith Mettananda
Senior Lecturer and Consultant Paediatrician
Department of Paediatrics Faculty of Medicine- University of Kelaniya Thalagolla Road Ragama
+94112961116
+94714805725

sachith.mettananda@kln.ac.lk

Contact Person for Public Queries

Dr Sachith Mettananda
Senior Lecturer and Consultant Paediatrician
Department of Paediatrics Faculty of Medicine- University of Kelaniya Thalagolla Road Ragama
+94112961116
+94714805725

sachith.mettananda@kln.ac.lk


Primary study sponsor/organization

Faculty of Medicine - University of Kelaniya

Thalagolla Road, Ragama, Sri Lanka.
Tel: +94112961116
Fax: 0112958337
Email: sachith.mettananda@kln.ac.lk
Website: http://www.kln.ac.lk

Secondary study sponsor (If any)

None





Trial Completion details


Do the investigators plan to share identified individual clinical trial participant-level data (IPD)?


IPD sharing plan description

Not Available


Study protocol available


Protocol version and date

Not Available


Protocol URL

Not Available


Results summary available

No


Date of posting results


Date of study completion


Final sample size


Date of first publication


Link to results


Brief summary of results