Pan African Clinical Trials Registry
South African Medical Research Council, South African Cochrane Centre
PO Box 19070, Tygerberg, 7505, South Africa
Telephone: +27 21 938 0506 / +27 21 938 0834 Fax: +27 21 938 0836
Email: pactradmin@mrc.ac.za Website: pactr.samrc.ac.za
Trial no.: PACTR201611001864290 Date of Approval: 12/11/2016
Trial Status: Registered in accordance with WHO and ICMJE standards
TRIAL DESCRIPTION
Public title Arginine supplementation in children with sickle cell crisis
Official scientific title Cardiovascular changes in sickle cell crisis and impact of arginine supplementation in vaso-occlusive crisis and acute chest syndrome
Brief summary describing the background and objectives of the trial 1.1 Introduction Sickle cell disease (SCD) is an inherited disorder of the haematological system affecting about 250 million people globally. About 50-90% of children with this condition die before adulthood. Sickle cell anaemia (SCA), the commonest and severest form of SCD, is frequently complicated by sickle cell crises such as vaso-occlusive crisis (VOC), acute chest syndrome, sequestration crisis, hyperhaemolytic crisis, central nervous system crisis, and aplastic crisis. 1.2 Role, dose and safety of arginine in sickle cell disease Serum arginine concentrations have been shown to drop from a mean of 53.6±4.6 µmol/l in steady state to a mean of 34.5±3.3µmol/l in children hospitalized for VOC. Administration of arginine improves outcome of sickle cell crisis. In two separate studies, Morris et al established the therapeutic dose and safety profile of L-arginine in SCD patients during both crisis and steady state. 2.0 RELEVANCE OF THE STUDY Nigeria has the largest number of children with SCA in the world and it is one of the highest non-infectious cardiopulmonary causes of mortality in Nigeria. Studies have shown that children with SCD have low plasma arginine especially during a crisis. Arginine therapy has been reported to decrease pain scores, limit the amount of narcotic use, and improves cardiac condition in children with crisis. 3.1 Research hypothesis Sickle cell crisis creates an additional burden on the already stressed myocardium in children with SCA and arginine supplementation improves pain control and cardiac sequelae sickle cell crisis. 3.2 Objective of the study To study the effect of sickle cell crisis on cardiovascular parameters and the impact of arginine supplementation on the pain and cardiac sequelae of severe VOC and ACS in children with SCA.
Type of trial RCT
Acronym (If the trial has an acronym then please provide)
Disease(s) or condition(s) being studied Haematological Disorders,Paediatrics,Sickle cell disease
Sub-Disease(s) or condition(s) being studied
Purpose of the trial Supportive care
Anticipated trial start date 01/12/2016
Actual trial start date
Anticipated date of last follow up 01/12/2017
Actual Last follow-up date
Anticipated target sample size (number of participants) 100
Actual target sample size (number of participants)
Recruitment status Recruiting
Publication URL
Secondary Ids Issuing authority/Trial register
M160326 Human Research Ethics Committee, Witwatersrand University, Johannesburg
STUDY DESIGN
Intervention assignment Allocation to intervention If randomised, describe how the allocation sequence was generated Describe how the allocation sequence/code was concealed from the person allocating the participants to the intervention arms Masking If masking / blinding was used
Factorial: participants randomly allocated to either no, one, some or all interventions simultaneously Randomised Permuted Block of Four Randomization Allocation was determined by the holder of the sequence who is not directly related to the study Masking/blinding used Outcome Assessors,Participants
INTERVENTIONS
Intervention type Intervention name Dose Duration Intervention description Group size Nature of control
Experimental Group Arginine supplementation 100mg/kg 8 hourly five days Oral administration of arginine 50 Placebo
Control Group Placebo-galactose 100mg/kg 8hourly five days 50 Placebo
ELIGIBILITY CRITERIA
List inclusion criteria List exclusion criteria Age Category Minimum age Maximum age Gender
Presence of HbSS Painful crisis with pain score of 7 and above Acute chest syndrome Allergy to arginine Hb concentration of 5g/dl and below Presence of congenital and acquired heart diseases Electrolyte derangement Patients with kidney and liver diseases Adolescent: 13 Year-18 Year,Child: 6 Year-12 Year,Preschool Child: 2 Year-5 Year 5 Year(s) 17 Year(s) Both
ETHICS APPROVAL
Has the study received appropriate ethics committee approval Date the study will be submitted for approval Date of approval Name of the ethics committee
Yes 28/04/2016 University of Abuja Teaching Hospital Health Research Ethics Committee
Ethics Committee Address
Street address City Postal code Country
University of Abuja Teaching Hospital Gwagwalada-Abuja 800001 Nigeria
OUTCOMES
Type of outcome Outcome Timepoint(s) at which outcome measured
Primary Outcome proportion of children with myocardial ischaemia, percentage change in mean Doppler estimated pulmonary artery pressure and percent reduction in total analgesic medications Pre-arginine supplementation Day 6 of commencement of arginine
Secondary Outcome 1. Changes in cardiac biomakers. 2. Changes in wall stress and ventricular functions. 3. Mean changes in Doppler estimated mean pulmonary artery pressure. 4. Changes in pain scores. 5. Time of crisis resolution. 6. Time from initiation of arginine supplementation to the last dose of parenteral analgesia Pre-arginine supplementation 6th day of commencement of arginine supplementation
RECRUITMENT CENTRES
Name of recruitment centre Street address City Postal code Country
University of Abuja Teaching Hospital Phase III, Gwagwalada Abuja 800001 Nigeria
National Hospital Abuja Abuja 800001 Nigeria
FUNDING SOURCES
Name of source Street address City Postal code Country
Tertiary Education Trust Fund University of Abuja Abuja 800001 Nigeria
SPONSORS
Sponsor level Name Street address City Postal code Country Nature of sponsor
Secondary Sponsor Tertiary Education Trust Fund University of Abuja Abuja 800001 Nigeria University
COLLABORATORS
Name Street address City Postal code Country
Peter Cooper University of the Witwatersrand Johannesburg South Africa
Antoinette Cilliers Chris Hanni Baragwanath Academic Hospital Soweto, Johannesburg South Africa
Claudia Morris 1760 Haygood Drive NE, W458 Atlanta GA GA 30322 United States of America
Oluseyi O. Oniyangi National Hospital Abuja 800001 Nigeria
Uche Nnebe-Agumadu University of Abuja Teaching Hospital, Gwagwalada, Abuja, Nigeria Gwagwalada 800001 Nigeria
CONTACT PEOPLE
Role Name Email Phone Street address
Principal Investigator Richard Onalo richardonalo@yahoo.com +234 803 701 7678 University of Abuja
City Postal code Country Position/Affiliation
Abuja 800001 Nigeria Senior lecturer/Consultant Paediatrician
Role Name Email Phone Street address
Public Enquiries Richard Onalo richardonalo@yahoo.com +234 803 701 7678 University of Abuja Teaching Hospital
City Postal code Country Position/Affiliation
Gwagwalada, Abuja 800001 Nigeria Consultant Paediatrician
Role Name Email Phone Street address
Scientific Enquiries Richard Onalo richardonalo@yahoo.com +234 803 701 7678 University of Abuja Teaching Hospital
City Postal code Country Position/Affiliation
Gwagwalada, Abuja 800001 Nigeria Consultant Paediatrician
REPORTING
Share IPD Description Additional Document Types Sharing Time Frame Key Access Criteria
URL Results Available Results Summary Result Posting Date First Journal Publication Date
Result Upload 1: Result Upload 2: Result Upload 3: Result Upload 4: Result Upload 5:
Result URL Hyperlinks Link To Protocol
Result URL Hyperlinks
Changes to trial information