Preventing Stroke Triggers in Children With Sickle Cell Anaemia in Mulago Hospital, Kampala (PREST ): a Randomized Control Trial

Summary

Sickle cell anaemia (SCA) is a common hereditary haemoglobin disorder in Africa. World wide it is estimated that about 300,000 newborns are born every year. Of which 75% of them live in Sub-saharan Africa (SSA). In Uganda, about 15,000 babies are born with sickle cell disease per year.

In Uganda, the stroke prevalence was found to be 6.2% in children admitted to the National referral hospital in Kampala. Notable between 21 to 30% of these children presented with co-morbidities such as anaemia, bacteraemia and painfull crisis. Stroke in SCA is mediated by several mechanism such as cellular adhesions, inflammatory markers, hemolysis associated oxidative stress and hemostatic activation. Stroke in SCA is primarily a large vessel stroke and the mechanisim state above lead to a narrowing of the lumen of the cerebral arteries Arterial ischaemic stroke which occurs frequently in children with SCA has been associated with bacterial infections. Recent studies have shown that minor infections such as flu like infections can play a critical role in the trigger of stroke in children.

Our hypothesis is that viral flu infections is a key trigger for the risk of stroke in children with SCA. Our objective is to prevent the occurrence of flu illnesses in children with SCA thereby reducing the risk for stroke in our population of children with SCA.

Methods: A randomized controlled double blinded study Study site: The study will be conducted at the Sickle Cell Clinic (SCC), Mulago Hospital. Inclusion criteria: will be ;age between 2 years and 12 years;All children whose parents will have consented and those above 7years will have to assent. Exclusion criteria: all children with previous strokes; children who have acute illness and are not clinically stable; any child with previous documented adverse event following immunization (AEFI).

Sample Size: Using Open EPI calculator for cohort studies we calculated a total sample size of 136 participant to achieve our objective. Using a 95% confidence interval, power of 80% and an unexposed outcome of 25% (4) using a ratio of 1:1. Each arm will have 68 participants. With anticipated 10% loss to follow up a total sample size of 150 with each arm having 75 participants.

Study utility: Globally, stroke triggers have been recently identified independent of the existing risk factors such as high cerebral velocity speeds on TCDs. Flues like illnesses have been reported to be stroke triggers in children with arterial ischaemic strokes worldwide.This study may influence the role of influenza vaccination in the prevention of stroke triggers in children with sickle cell anaemia. It will also add to the existing modalities which have helped to reduce the incidence of stroke amongst this high risk group of children with

Conditions

• Preventing Stroke in Sickle Cell Anaemia

Interventions

BIOLOGICAL

Influenza vaccine

The randomized FLUVACS trial demonstrated the benefits of influenza vaccination in the prevention of cardiovascular death. In the VIPS study the risk for acute ischaemic stroke (AIS) in children increased by 6-fold compared to the baseline population. It was postulated that infections and in particular upper respiratory tract infections acts as a stroke trigger in a child who is otherwise predisposed to stroke and why it would occur at a particular point in that child's life. It should be noted that major infections such as meningitis have been causes of stroke while this study has shown that minir infections can also act as a trigger for stroke in adults

Sponsors & Collaborators

• Makerere University

  lead OTHER

Study Design

Allocation

RANDOMIZED

Purpose

PREVENTION

Masking

QUADRUPLE

Model

PARALLEL

Eligibility

Min Age

2 Years

Max Age

12 Years

Sex

ALL

Healthy Volunteers

No

Timeline & Regulatory

Start

2018-08-22

Primary Completion

2019-09-30

Completion

2019-12-31

Countries

• Uganda

Study Locations