Different Treatment Modalities in the Management of the Painful Crisis in Pediatric Sickle- Cell Anemia

NCT04301336 | Completed Phase 2

• 1 other identifier: Novel TTT of pedia VOC/SCA
• Study Type: interventional
• Target: 350
• Locations: 2 countries
• Sites: 4

Brief Summary

The aim of the present study is comparing the effectiveness of different treatment regimens for investigating the therapeutic potential for each one in management of Vaso-occlusive pain in pediatric sickle cell disease. In addition, investigators apply the Cost-effectiveness analysis (CEA) as a form of economic analysis that compares the relative costs and outcomes (effects) for different treatment regimens on vaso-occlusive painful crisis.

Conditions

Vaso-occlusive Crisis; Sickle Cell Disease; Sickle Cell Anemia in Children

Keywords

omega3; Vaso-occlusive painful crisis; Pediatric sickle cell anemia; comparative effective analysis in VOC; Anti-inflammatory effect of Vit-D; Anti-hemolytic effect of Vit-D; Anti-hyperlipidemia of Vit-D; effect of omega-3 on blood rheology; effect of omega-3 on blood viscosity; Antiaggregation effect of omega-3; Anti-inflammatory effect of statins; Anti-inflammatory effect of zinc supplements; effect of zinc supplements on blood viscosity; effect of zinc supplements on blood rheology; Antiaggregation effect of zinc supplements; pediatric sickle cell disease

Outcome Measures

Primary Outcomes (16)

• C-reactive protein mg/L

  C-reactive protein milligrams per deciliter

  10 months

• Hematocrit %

  Hematocrit level in percentage value

  10 months

• Fibrinogen mg/dl

  Fibrinogen concentration in milligrams per deciliter

  10 months

• Total cholesterol Mg/dl

  Total cholesterol milligrams per deciliter

  10 months

• HDL cholesterol Mg/dl

  HDL cholesterol milligrams per deciliter

  10 months

• LDL cholesterol Mg/dl

  LDL cholesterol milligrams per deciliter

  10 months

• Triglycerides Mg/dl

  Triglycerides milligrams per deciliter

  10 months

• leukocytes count μl

  leukocytes in microliter

  10 months

• hemoglobin (Hbg) g/dL

  hemoglobin (Hbg) gram/deciliter

  10 months

• White blood cells count

  White blood cells count in a cubic milliliter of blood

  10 months

• Lactic acid dehydrogenase U/L

  Lactic acid dehydrogenase unit per litter

  10 months

• Reticulocyte count %

  Reticulocyte count percentage

  10 months

• Red blood cell (erythrocyte ) sedimentation rate mm/hr

  erythrocyte sedimentation rate in millimeters (mm) per one hour(hr)

  10 months

• lymphocyte count µL

  lymphocyte count in 1 microliter (µL) of blood

  10 months

• Granulocyte absolute count cells/microliter

  Granulocyte cells numbers in microliter

  10 months

• Granulocytes,percentage (GR, pct)

  percentage of white blood cells with granules in percentage

  10 months

Study Arms (5)

Omega-3 experimental group

EXPERIMENTAL

50 patients from each participating hospital that will receive Omega-3 supplementation (300-400mg EPA \& 200-300mg DHA) per day for 8 consecutive months up to 10 months. in addition to the experimental treatment, this group will receive the traditional treatment of hydroxyurea, Folic acid, pain killer plus regular blood transfusion with a dose de-escalation methods till efficacy of experimental treatment proved.

Drug: Omega 3; Drug: Hydroxy Urea; Drug: Folic Acid Supplementation; Drug: Morphine Sulfate; Procedure: blood transfusion session

Vit-D experimental group

EXPERIMENTAL

50 patients from each participating hospital that will receive Vit-D medication (1500 IU to 3500 IU ) per day for 8 consecutive months up to 10 months. in addition to the experimental treatment, this group will receive the traditional treatment of hydroxyurea, Folic acid, pain killer plus regular blood transfusion with a dose de-escalation methods till efficacy of experimental treatment proved.

Drug: Vit D; Drug: Hydroxy Urea; Drug: Folic Acid Supplementation; Drug: Morphine Sulfate; Procedure: blood transfusion session

Zinc supplements experimental group

EXPERIMENTAL

50 patients from each participating hospital that will receive Zinc supplements (15 mg to 50 mg ) per day for 8 consecutive months up to 10 months. in addition to the experimental treatment, this group will receive the traditional treatment of hydroxyurea, Folic acid, pain killer plus regular blood transfusion with a dose de-escalation methods till efficacy of experimental treatment proved.

Drug: Zinc sulfate; Drug: Hydroxy Urea; Drug: Folic Acid Supplementation; Drug: Morphine Sulfate; Procedure: blood transfusion session

Statin experimental group

EXPERIMENTAL

50 patients from each participating hospital that will receive Simvastatin orally (20 mg to 40 mg ) per day for 8 consecutive months up to 10 months. in addition to the experimental treatment, this group will receive the traditional treatment of hydroxyurea, Folic acid, pain killer plus regular blood transfusion with a dose de-escalation methods till efficacy of experimental treatment proved.

Drug: Statins (Cardiovascular Agents); Drug: Hydroxy Urea; Drug: Folic Acid Supplementation; Drug: Morphine Sulfate; Procedure: blood transfusion session

Ordinary hospital treatment group

ACTIVE COMPARATOR

50 patients from each participating hospital that will receive the ordinary treatment of Hydroxyurea (20 mg/kg/day) with monitoring blood count every 2 weeks maximum daily dose: (40 mg/kg/day) for 8 consecutive months up to 10 months. in addition, Folic Acid dose of 0.5 to 1 mg daily for 3 to 4 weeks until definite hematologic response in addition, Morphine medication as a pain killer is administered, if Patient weight \<50 kg: Opioid naïve: Initial: 0.05 mg/kg/dose; usual maximum initial dose: 1 to 2 mg/dose. This group received regular blood transfusion session.

Drug: Hydroxy Urea; Drug: Folic Acid Supplementation; Drug: Morphine Sulfate; Procedure: blood transfusion session

Interventions

Omega 3 DRUG

Omega-3 supplementation (300-400mg EPA \& 200-300mg DHA) per day for 8 consecutive months up to 10 months

Also known as: omega-3 supplementation capsules

Omega-3 experimental group

Vit D DRUG

50 patients from each participating hospital that will receive Vit-D medication (1500 IU to 3500 IU ) per day for 8 consecutive months up to 10 months. in addition to the experimental treatment, this group will receive the traditional treatment of hydroxyurea, Folic acid, pain killer plus regular blood transfusion with a dose de-escalation methods till efficacy of experimental treatment proved.

Also known as: Vit-D medication oral drops

Vit-D experimental group

Zinc sulfate DRUG

50 patients from each participating hospital that will receive Zinc supplements (15 mg to 50 mg ) per day for 8 consecutive months up to 10 months. in addition to the experimental treatment, this group will receive the traditional treatment of hydroxyurea, Folic acid, pain killer plus regular blood transfusion with a dose de-escalation methods till efficacy of experimental treatment proved.

Also known as: Zinc tablet medication

Zinc supplements experimental group

Statins (Cardiovascular Agents) DRUG

50 patients from each participating hospital that will receive Simvastatin orally (20 mg to 40 mg ) per day for 8 consecutive months up to 10 months. in addition to the experimental treatment, this group will receive the traditional treatment of hydroxyurea, Folic acid, pain killer plus regular blood transfusion with a dose de-escalation methods till efficacy of experimental treatment proved.

Also known as: Simvastatin 20mg

Statin experimental group

Hydroxy Urea DRUG

50 patients from each participating hospital that will receive the ordinary treatment of Hydroxyurea (20 mg/kg/day) with monitoring blood count every 2 weeks maximum daily dose: (40 mg/kg/day) for 8 consecutive months up to 10 months.

Also known as: Hydroxy Urea tablet medication 20mg/kg/day

Omega-3 experimental group; Ordinary hospital treatment group; Statin experimental group; Vit-D experimental group; Zinc supplements experimental group

Folic Acid Supplementation DRUG

Folic Acid dose of 0.5 to 1 mg daily for 3 to 4 weeks until definite hematologic response

Also known as: Folic Acid tablet medication 1mg/day

Omega-3 experimental group; Ordinary hospital treatment group; Statin experimental group; Vit-D experimental group; Zinc supplements experimental group

Morphine Sulfate DRUG

Morphine medication as a pain killer is administered, if Patient weight \<50 kg: Opioid naïve: Initial: 0.05 mg/kg/dose; usual maximum initial dose: 1 to 2 mg/dose.

Also known as: Morphine Sulfate intra venous medication

Omega-3 experimental group; Ordinary hospital treatment group; Statin experimental group; Vit-D experimental group; Zinc supplements experimental group

blood transfusion session PROCEDURE

Regular blood transfusion session based on patient hematological profile starts from one session every 2 weeks.

Omega-3 experimental group; Ordinary hospital treatment group; Statin experimental group; Vit-D experimental group; Zinc supplements experimental group

Eligibility Criteria

• Age: 5 Years - 15 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Any case with the full manifestation of sickle cell disease accompanied by acute painful crisis aged from 5-15 years old.

You may not qualify if:

• The presence of any other chronic illness.
• Patient age\>18 years old or \< 3 years old.
• Patients with hepatic diseases including cholestasis hepatic encephalopathy and jaundice.
• Patients with renal impairment
• Diabetic patients

Sponsors & Collaborators

• Beni-Suef University: lead
• Benisuef university hospital: collaborator
• University of Arizona: collaborator
• Maternity and Children Hospital, Makkah: collaborator

Study Sites (4)

Faculty of medicine, Beni-suef univeristy - Beni-Seuf university hospital

Banī Suwayf, Egypt

Location

Faculty of Pharmacy, Beni-Suef university

Banī Suwayf, Egypt

Location

Health insurance hospital

Banī Suwayf, Egypt

Location

Maternity and Children hospital

Mecca, Saudi Arabia

Location

MeSH Terms

Conditions

Vaso-Occlusive Crises; Anemia, Sickle Cell

Interventions

Docosahexaenoic Acids; Zinc Sulfate; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Cardiovascular Agents; Simvastatin; Hydroxyurea; Morphine

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Anemia; Hematologic Diseases; Hemic and Lymphatic Diseases; Hemoglobinopathies; Genetic Diseases, Inborn; Congenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

Fatty Acids, Omega-3; Dietary Fats, Unsaturated; Dietary Fats; Fats; Lipids; Fatty Acids, Unsaturated; Fatty Acids; Fish Oils; Oils; Sulfates; Sulfuric Acids; Sulfur Acids; Sulfur Compounds; Inorganic Chemicals; Zinc Compounds; Anticholesteremic Agents; Hypolipidemic Agents; Antimetabolites; Molecular Mechanisms of Pharmacological Action; Pharmacologic Actions; Chemical Actions and Uses; Enzyme Inhibitors; Lipid Regulating Agents; Therapeutic Uses; Lovastatin; Naphthalenes; Polycyclic Aromatic Hydrocarbons; Hydrocarbons, Aromatic; Hydrocarbons, Cyclic; Hydrocarbons; Organic Chemicals; Polycyclic Compounds; Urea; Amides; Morphine Derivatives; Morphinans; Opiate Alkaloids; Alkaloids; Heterocyclic Compounds; Heterocyclic Compounds, Bridged-Ring; Heterocyclic Compounds, 4 or More Rings; Heterocyclic Compounds, Fused-Ring; Phenanthrenes

Study Officials

• John E. Murphy [Professor of Pharmacy Practice and Science], PharmD

  University of Arizona, College of Pharmacy

  STUDY DIRECTOR

• Mohamed H Meabad [Prof of Pediatrics], M.D

  Beni-Suef University, Faculty of medicine

  STUDY DIRECTOR

• AHMED A ALBERRY [Assistant prof of clinical pharmacology], M.D

  Beni-Suef University, Faculty of medicine

  STUDY DIRECTOR

• RAGHDA R SAYED [Lecturer of Clinical Pharmacy, Ph.D.

  Beni-Suef University, Faculty of Pharmacy

  STUDY DIRECTOR

• Shaimaa M Nashat Sayed Abdelhalim, Ph.D Student

  Beni-Suef University, Faculty of Pharmacy

  PRINCIPAL INVESTIGATOR

• Ahmed F Mahmoud Hussein, MS.c

  Beni-Suef Health insurance hospital

  STUDY DIRECTOR

Study Design

• Study Type: interventional
• Phase: phase 2
• Allocation: RANDOMIZED
• Masking: DOUBLE
• Who Masked: PARTICIPANT, CARE PROVIDER
• Purpose: TREATMENT
• Intervention Model: PARALLEL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr.Shaimaa Mahmoud Nashat Sayed Abdelhalim, Ph.D. Researcher and Principal Investigator

Model Details: Four experimental groups, one control group

Study Record Dates

• First Submitted: March 6, 2020
• First Posted: March 10, 2020
• Study Start: November 1, 2019
• Primary Completion: November 1, 2020
• Study Completion: December 10, 2020
• Last Updated: January 27, 2021

Record last verified: 2021-01

Locations

EG (3); SA (1)