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

Comparative Effectiveness of the Different Treatment Modalities for Management of Vaso-occlusive Painful Crisis in Pediatric Sickle Cell Disease

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.

Study Overview

• Status: Completed
• Conditions: Sickle Cell Disease; Vaso-occlusive Crisis; Sickle Cell Anemia in Children
• Intervention / Treatment: Drug: Omega 3; Procedure: blood transfusion session; Drug: Hydroxy Urea; Drug: Folic Acid Supplementation; Drug: Morphine Sulfate; Drug: Vit D; Drug: Zinc sulfate; Drug: Statins (Cardiovascular Agents)

Detailed Description

"Sickle cell disease is an inherited blood disorder characterized by defective hemoglobin (a protein in red blood cells that carries oxygen to the tissues of the body).

Sickle cell disease involves the red blood cells, or hemoglobin, and their ability to carry oxygen. Normal hemoglobin cells are smooth, round, and flexible, like the letter "O," so they can move through the vessels in our bodies easily. Sickle cell hemoglobin cells are stiff and sticky and form into the shape of a sickle, or the letter "C," when they lose their oxygen. These sickle cells tend to cluster together and cannot easily move through the blood vessels. The cluster causes a blockage in small arteries or capillaries and stops the movement of healthy, normal oxygen-carrying blood. This blockage is what causes the painful and damaging complications of sickle cell disease".

"Acute vaso-occlusive crisis (VOC) is a hallmark of sickle cell disease (SCD). Multiple complex pathophysiological processes can result in pain during a VOC. Despite significant improvements in the understanding and management of SCD, little progress has been made in the management of pain in SCD, although new treatments are being explored".

The Painful Episodes:

"The day-to-day management of sickle cell disease often equates with the management of acute and chronic pain. Patients manage many painful events at home so that hospital visits underestimate the frequency of pain

Acute painful episodes are the most commonly encountered vaso-occlusive events in patients of all ages. Presumed to be caused by sickle vaso-occlusion, pain often starts in young children as the hand-foot syndrome or dactylitis, a painful swelling of hands and feet due to inflammation of the metacarpal and metatarsal periosteum. Painful episodes, which last from hours to many days, usually occur with little warning and a clear precipitating event is not often found.

• Study Type: Interventional
• Enrollment (Actual): 350
• Phase: Phase 2; Phase 3

Contacts and Locations

Study Locations

• Egypt
  • Banī Suwayf, Egypt
    • Faculty of pharmacy, Beni-Suef University
  • Banī Suwayf, Egypt
    • Health insurance hospital
  • Banī Suwayf, Egypt
    • Faculty of medicine, Beni-suef univeristy - Beni-Seuf university hospital
• Saudi Arabia
  • Mecca, Saudi Arabia
    • Maternity and Children hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 5 years to 15 years (Child)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

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

Exclusion Criteria:

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

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: Randomized
• Interventional Model: Parallel Assignment
• Masking: Double

Number of Arms

5

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Omega-3 experimental group; 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; Omega-3 supplementation (300-400mg EPA & 200-300mg DHA) per day for 8 consecutive months up to 10 months; Other Names: omega-3 supplementation capsules; Procedure: blood transfusion session; Regular blood transfusion session based on patient hematological profile starts from one session every 2 weeks.; Drug: Hydroxy Urea; 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.; Other Names: Hydroxy Urea tablet medication 20mg/kg/day; Drug: Folic Acid Supplementation; Folic Acid dose of 0.5 to 1 mg daily for 3 to 4 weeks until definite hematologic response; Other Names: Folic Acid tablet medication 1mg/day; Drug: Morphine Sulfate; 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.; Other Names: Morphine Sulfate intra venous medication
Experimental: Vit-D experimental group; 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.	Procedure: blood transfusion session; Regular blood transfusion session based on patient hematological profile starts from one session every 2 weeks.; Drug: Hydroxy Urea; 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.; Other Names: Hydroxy Urea tablet medication 20mg/kg/day; Drug: Folic Acid Supplementation; Folic Acid dose of 0.5 to 1 mg daily for 3 to 4 weeks until definite hematologic response; Other Names: Folic Acid tablet medication 1mg/day; Drug: Morphine Sulfate; 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.; Other Names: Morphine Sulfate intra venous medication; Drug: Vit D; 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.; Other Names: Vit-D medication oral drops
Experimental: Zinc supplements experimental group; 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.	Procedure: blood transfusion session; Regular blood transfusion session based on patient hematological profile starts from one session every 2 weeks.; Drug: Hydroxy Urea; 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.; Other Names: Hydroxy Urea tablet medication 20mg/kg/day; Drug: Folic Acid Supplementation; Folic Acid dose of 0.5 to 1 mg daily for 3 to 4 weeks until definite hematologic response; Other Names: Folic Acid tablet medication 1mg/day; Drug: Morphine Sulfate; 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.; Other Names: Morphine Sulfate intra venous medication; Drug: Zinc sulfate; 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.; Other Names: Zinc tablet medication
Experimental: Statin experimental group; 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.	Procedure: blood transfusion session; Regular blood transfusion session based on patient hematological profile starts from one session every 2 weeks.; Drug: Hydroxy Urea; 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.; Other Names: Hydroxy Urea tablet medication 20mg/kg/day; Drug: Folic Acid Supplementation; Folic Acid dose of 0.5 to 1 mg daily for 3 to 4 weeks until definite hematologic response; Other Names: Folic Acid tablet medication 1mg/day; Drug: Morphine Sulfate; 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.; Other Names: Morphine Sulfate intra venous medication; Drug: Statins (Cardiovascular Agents); 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.; Other Names: Simvastatin 20mg
Active Comparator: Ordinary hospital treatment group; 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.	Procedure: blood transfusion session; Regular blood transfusion session based on patient hematological profile starts from one session every 2 weeks.; Drug: Hydroxy Urea; 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.; Other Names: Hydroxy Urea tablet medication 20mg/kg/day; Drug: Folic Acid Supplementation; Folic Acid dose of 0.5 to 1 mg daily for 3 to 4 weeks until definite hematologic response; Other Names: Folic Acid tablet medication 1mg/day; Drug: Morphine Sulfate; 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.; Other Names: Morphine Sulfate intra venous medication

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
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
C-reactive protein mg/L	C-reactive protein milligrams per deciliter	10 months
hemoglobin (Hbg) g/dL	hemoglobin (Hbg) gram/deciliter	10 months
leukocytes count μl	leukocytes in microliter	10 months
Lactic acid dehydrogenase U/L	Lactic acid dehydrogenase unit per litter	10 months
Reticulocyte count %	Reticulocyte count percentage	10 months
White blood cells count	White blood cells count in a cubic milliliter of blood	10 months
Hematocrit %	Hematocrit level in percentage value	10 months
Fibrinogen mg/dl	Fibrinogen concentration in milligrams per deciliter	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

Collaborators and Investigators

• Sponsor: Beni-Suef University
• Collaborators: University of Arizona; Maternity and Children Hospital, Makkah; Benisuef university hospital
• Investigators: Study Director: Mohamed H Meabad [Prof of Pediatrics], M.D, Beni-Suef University, Faculty of medicine; Study Director: Ahmed F Mahmoud Hussein, MS.c, Beni-Suef Health insurance hospital; Study Director: John E. Murphy [Professor of Pharmacy Practice and Science], PharmD, University of Arizona, College of Pharmacy; 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; Principal Investigator: Shaimaa M Nashat Sayed Abdelhalim, Ph.D Student, Beni-Suef University, Faculty of Pharmacy

Study record dates

Study Major Dates

• Study Start (Actual): November 1, 2019
• Primary Completion (Actual): November 1, 2020
• Study Completion (Actual): December 10, 2020

Study Registration Dates

• First Submitted: March 6, 2020
• First Submitted That Met QC Criteria: March 6, 2020
• First Posted (Actual): March 10, 2020

Study Record Updates

• Last Update Posted (Actual): January 27, 2021
• Last Update Submitted That Met QC Criteria: January 25, 2021
• Last Verified: January 1, 2021

More Information

Terms related to this study

• 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
• Additional Relevant MeSH Terms: Hematologic Diseases; Genetic Diseases, Inborn; Anemia, Hemolytic, Congenital; Anemia, Hemolytic; Hemoglobinopathies; Anemia; Anemia, Sickle Cell; Physiological Effects of Drugs; Molecular Mechanisms of Pharmacological Action; Central Nervous System Depressants; Peripheral Nervous System Agents; Nucleic Acid Synthesis Inhibitors; Enzyme Inhibitors; Analgesics; Sensory System Agents; Antimetabolites; Antineoplastic Agents; Dermatologic Agents; Trace Elements; Micronutrients; Anticholesteremic Agents; Hypolipidemic Agents; Lipid Regulating Agents; Hydroxymethylglutaryl-CoA Reductase Inhibitors; Analgesics, Opioid; Narcotics; Vitamins; Hematinics; Antisickling Agents; Astringents; Hydroxyurea; Morphine; Folic Acid; Vitamin B Complex; Simvastatin; Zinc; Zinc Sulfate
• Other Study ID Numbers: Novel TTT of pedia VOC/SCA

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No