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Bronchiolitis; Respiratory Syncytial VirusPhase 1NCT03436225

Steroid Therapy in Acute Bronchiolitis A New Old Line of Therapy.

A Phase 1 study testing Dexamethasone orally., Dexamethasone parenteral. and Inhaled nebulized Budesonide. in people with Bronchiolitis; Respiratory Syncytial Virus, run by Assiut University.

Unknown status

Status not confirmed. The sponsor has not verified this record for over two years, so it may be out of date.

Official record
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Trial summary

The aim of the present study is to evaluate the efficacy of steroid therapy and hospital stay in patients with acute bronchiolitis at assiut university children hospital. Read more about this study

Who is it for?
Ages 3 months to 2 years
What is being tested?
Dexamethasone orally., Dexamethasone parenteral. and Inhaled nebulized Budesonide.
Could I receive a placebo?
No, everyone receives an active treatment
How many people
80 participants
Where
No sites listed yet
Study dates
Feb 2019to Mar 2019
Phase
Phase 1
Are there results?
None posted in the registry

Key requirements

Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.

  • Ages 3 months to 2 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • Infants and young children aged from 3 months to 2 years with acute bronchiolitis.
  • Infants aged <12 months with respiratory rate over 60 breaths/min, childrens aged >12months with respiratory rate over 50 breaths/min.
  • Patients with an O2- saturation, breathing room air, under 95%.
  • Patients with apathy and/or refusal to eat.
  • Patients with normal white blood cell count for age.
  • Full term babies without chronic disease.

Who cannot join

  • Infants aged < 3 months, children aged >2 years
  • known or suspected asthma (by observing the good response to first dose of salbutamol nebulization especially among those with personal history of atopy).
  • Proven or suspected acute bacterial infection.
  • Presence of symptoms more than 7 days.
  • Previous treatment with corticosteroid by any route within 2 weeks.
  • Having a contra- indication to corticosteroid.
Show all 12Show fewer
  • Severe cases requiring initial admission to intensive care unit with endotracheal intubation (in order to reduce confounding factors such as nosocomial infection or complication due to mechanical ventilation).
  • A previous history of intubation.
  • Premature babies (due to possible respiratory problems associated with prematurity).
  • Children with chronic cardiopulmonary diseases (Bronchopulmonary- dysplasia , Congenital Heart Disease and Cystic fibrosis)
  • Children with immunodeficiencies .
  • Children with neuromuscular disease.

About this study

The aim of the present study is to evaluate the efficacy of steroid therapy and hospital stay in patients with acute bronchiolitis at assiut university children hospital.

Read the detailed description

Bronchiolitis is an acute lower respiratory tract infection in early childhood.A subcommittee of the American Academy of Pediatrics (AAP) together with the European Respiratory Society (ERS) underlined that is a clinical diagnosis, recognized as "a constellation of clinical symptoms and signs including a viral upper respiratory prodrome followed by increased respiratory effort and wheezing in children less than 2 years of age".

Bronchiolitis is the common reason for hospitalization of children in many countries, challenging both economy, area and staffing in pediatric departments. A substantial proportion of children will experience at least one episode with bronchiolitis, and as much as 2-3% of all children will be hospitalized with bronchiolitis during their first year of life. Bronchiolitis is the most common medical reason for admission of children to intensive care units (ICU) particularly those with risk Factors will have a severe course of bronchiolitis, providing challenges regarding ventilation, fluid balance and general support This may be a particular challenge for ICUs without a specialized pediatric section.

Many respiratory viruses have been associated with acute viral bronchiolitis although Respiratory Syncytial Virus (RSV) remains the most common identified virus causing bronchiolitis, occurring in epidemics during winter months.The infection starts in the upper respiratory tract, spreading to the lower airways within few days.The inflammation in the bronchioles is characterized by a peri-bronchial infiltration of white blood cell types, mostly mono nuclear cells, and oedema of the submucosa and adventitia. Damage may occur by a direct viral injury to the respiratory airway epithelium, or indirectly by activating immune responses. Oedema, mucus secretion, and damage of airway epithelium with necrosis may cause partial or total airflow obstruction, distal air trapping, atelectasis and a ventilation perfusion mismatch leading to hypoxemia and increased work of breathing. Smooth-muscle constriction seems to play a minor role in the pathologic process of bronchiolitis.

Risk factors for bronchiolitis are male gender, a history of prematurity, young age, being born in relation to the RSV season, pre-existing disease such as broncho pulmonary- dysplasia , underlying chronic lung disease , neuromuscular disease, congenital heart- disease , exposure to environmental tobacco smoke , high parity, young maternal age, short duration/no breast feeding , maternal asthma and poor socioeconomic factors.

Bronchiolitis often starts with rhinorrhoea and fever, thereafter gradually increasing with signs of a lower respiratory tract infection including tachypnoea, wheezing and cough. Very young children, particularly those with a history of prematurity, may appear with apnea as their major symptom.Feeding problems are common.

On clinical examination, the major finding in the youngest children may be fine inspiratory crackles on auscultation, whereas high-pitched expiratory wheeze may be prominent in older children. By observation, the infants may have increased respiratory rate, chest movements, prolonged expiration, recessions, use of accessory muscles, cyanosis and decreased general condition.

No routine laboratory or radio graphic diagnostic tests for bronchiolitis except for pulse oxymetry , have been shown to have a substantial impact on the clinical course of bron- chiolitis , and recent guidelines and evidence-based reviews recommend that no diagnostic tests are used routinely.

The present study describes the efficacy of steroid therapy in patients with acute bronchiolitis. Theoretically, corticosteroid, an anti-inflammatory agent, should be helpful in the treatment of bronchiolitis because airway inflammation and edema are the main pathophysiologies. Recent evidence has shown elevation of interleukins and other inflammatory mediators in the respiratory tracts of children with acute bronchiolitis. Eosinophil cationic protein, implicated in the pathogenesis of asthma, was found to have a significant role in RSV bronchiolitis. Most of these mediators could be found during the period of virus replication.The clinical effect of dexamethasone, with a long half -life of 36-72 hr, may peak after 3-4 hr of treatment. Corticosteroids widely used in different routes in the treatment of acute bronchiolitis:

Dexamethasone injection used in hospitalized children with acute bronchiolitis showed significantly reduction in the mean respiratory distress duration, mean duration of oxygen therapy and the mean length of hospital stay.

Oral dexamethasone used in pediatric out patients with acute bronchiolitis produced demonstrable clinical improvement in the initial 4 hr of treatment and reduced the hospitalization rate.

Corticosteroid inhalation therapy used in RSV- bronchiolitis showed evidence of prolonged positive effects in reduction of the incidence of subsequent respiratory symptoms in the near future. However, the best and sufficient length of the treatment period, as well as the dose of the inhaled steroid, need to be determined..

Fluticasone propionate, a potent corticosteroid, has been demonstrated in vitro to inhibit virus-induced chemokine production by airway cells in patients infected with Respiratory Syncytial Virus. However, the inhibition was found to take at least 48 hr to reach its full effect.

Being tested
Dexamethasone orally., Dexamethasone parenteral., Inhaled nebulized Budesonide., Inhaled nebulized salbutamol.
Keywords
steroid therapy.
Medical subject headings
Bronchiolitis

What participants receive

What participants receive. In a randomised study each person is assigned to one group by chance.

  • Dexamethasone orally.Drug

    Also called Apidone syrup., Phenadone syrup.

    Administered orally (0.15mg /kg / dose) twice daily for 3 to 5 days.

  • Dexamethasone parenteral.Drug

    Also called Fortecortin 8 mg /2 ml ampoule i.v /i.m injection .

    Administered parenteral (0.15mg /kg / dose) twice daily for 3 to 5 days.

  • Inhaled nebulized Budesonide.Drug

    Also called Pulmicorte respules1 mg /2 ml.

    Administered for inhalation (1 mg/ 2ml) twice daily for 3 to 5 days.

  • Inhaled nebulized salbutamol.Drug

    Also called Farcoline respirator 0,5% solution.

    Administered for inhalation (0.15mg /kg / dose) daily every 6-8hrs

Study groups in NCT03436225
Study groupRoleWhat they receive
Group oneOtherGroup one will receive dexamethasone orally (0.15mg /kg / dose) twice daily for 3 to 5 days.
Receives: Drug: Dexamethasone orally.
Group twoOtherGroup two will receive dexamethasone parenteral (0.15mg /kg /dose) twice daily for 3 to 5 days.
Receives: Drug: Dexamethasone parenteral.
Group threeOtherGroup three will receive inhaled nebulized budesonide (1 mg/2ml) twice daily for 3 to 5 days.
Receives: Drug: Inhaled nebulized Budesonide.
Group fourOtherGroup four will receive symptomatic treatment in form of inhaled nebulized salbutamol(0.15mg/kg/ dose) daily every 6-8 hours.
Receives: Drug: Inhaled nebulized salbutamol.

What is being measured

The primary outcome is the main question the study is designed to answer.

  1. Resolution of respiratory distress.

    A total clinical score ≤ 3 and oxygen saturation ≥ 95 % at room air together with respiratory score of 0 or 1, a wheezing score of 0 or 1, and a retraction muscle score of 0 or 1

    Measured: <7 days

Secondary outcomes (3)
  1. Reduction of mean duration of symptoms.

    Improvement of respiratory symptoms within fewer days .

    Measured: <7 days

  2. Reduction of duration of oxygen therapy.

    Reduction the need for more oxygen therapy .

    Measured: <7 days

  3. Reduction of average Length of hospital stay.

    Decrease Length of hospital stay.

    Measured: <7 days

Timeline

From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.

  1. First posted19 Feb 2018
  2. Study startFeb 2019 (estimated)
  3. Primary completionFeb 2019 (estimated)
  4. Study completionMar 2019 (estimated)

Resources

More details

For doctors and researchers: how the study is designed, who runs it, and its registry IDs.

Study design
Study type
Interventional
Phase
Phase 1
Primary purpose
Treatment
Allocation
Randomised
Intervention model
Crossover
Masking
None (open label)
Enrolment
80 participants (estimated)
IDs, dates and publications
ClinicalTrials.gov ID
NCT03436225
Sponsor's protocol ID
Steroid in bronchiolitis.
Status last verified
Jan 2019
First submitted
12 Feb 2018
Last updated
9 Jan 2019
Results posted
No
Data monitoring committee
No
FDA-regulated drug
No
FDA-regulated device
No

Publications

  • Schimmer BP, Parker KL. Adrenocorticotropic hormone; adrenocortical steroids and their synthetic analogs; inhibitor of the synthesis and actions of adrenocortical hormones. In: Hardman JG, Limbird LE, Molinoff PB, Ruddon RW, Gilman AG,editors. Goodman & Gilman's the pharmacological basis of therapeutics, 9th edition. New York: McGraw-Hill; 1996.pp 1459-1485.

  • GOODWIN A. An uncontrolled assessment of nebulized budesonide in the treatment of acute bronchiolitis. Br J Clin Res 1995: 6: 113±9.

  • Nagakumar P, Doull I. Current therapy for bronchiolitis. Arch Dis Child. 2012 Sep;97(9):827-30. doi: 10.1136/archdischild-2011-301579. Epub 2012 Jun 25.

    PubMed 22734014
  • American Academy of Pediatrics Subcommittee on Diagnosis and Management of Bronchiolitis. Diagnosis and management of bronchiolitis. Pediatrics. 2006 Oct;118(4):1774-93. doi: 10.1542/peds.2006-2223.

    PubMed 17015575
  • Stockman LJ, Curns AT, Anderson LJ, Fischer-Langley G. Respiratory syncytial virus-associated hospitalizations among infants and young children in the United States, 1997-2006. Pediatr Infect Dis J. 2012 Jan;31(1):5-9. doi: 10.1097/INF.0b013e31822e68e6.

    PubMed 21817948
  • Choi J, Lee GL. Common pediatric respiratory emergencies. Emerg Med Clin North Am. 2012 May;30(2):529-63, x. doi: 10.1016/j.emc.2011.10.009. Epub 2011 Dec 17.

    PubMed 22487117
  • Zorc JJ, Hall CB. Bronchiolitis: recent evidence on diagnosis and management. Pediatrics. 2010 Feb;125(2):342-9. doi: 10.1542/peds.2009-2092. Epub 2010 Jan 25.

    PubMed 20100768
  • Wainwright C. Acute viral bronchiolitis in children- a very common condition with few therapeutic options. Paediatr Respir Rev. 2010 Mar;11(1):39-45; quiz 45. doi: 10.1016/j.prrv.2009.10.001. Epub 2009 Nov 26.

    PubMed 20113991
  • Carroll KN, Gebretsadik T, Griffin MR, Wu P, Dupont WD, Mitchel EF, Enriquez R, Hartert TV. Increasing burden and risk factors for bronchiolitis-related medical visits in infants enrolled in a state health care insurance plan. Pediatrics. 2008 Jul;122(1):58-64. doi: 10.1542/peds.2007-2087.

    PubMed 18595987
  • Murray J, Bottle A, Sharland M, Modi N, Aylin P, Majeed A, Saxena S; Medicines for Neonates Investigator Group. Risk factors for hospital admission with RSV bronchiolitis in England: a population-based birth cohort study. PLoS One. 2014 Feb 26;9(2):e89186. doi: 10.1371/journal.pone.0089186. eCollection 2014.

    PubMed 24586581
  • Bordley WC, Viswanathan M, King VJ, Sutton SF, Jackman AM, Sterling L, Lohr KN. Diagnosis and testing in bronchiolitis: a systematic review. Arch Pediatr Adolesc Med. 2004 Feb;158(2):119-26. doi: 10.1001/archpedi.158.2.119.

    PubMed 14757603
  • Sheeran P, Jafri H, Carubelli C, Saavedra J, Johnson C, Krisher K, Sanchez PJ, Ramilo O. Elevated cytokine concentrations in the nasopharyngeal and tracheal secretions of children with respiratory syncytial virus disease. Pediatr Infect Dis J. 1999 Feb;18(2):115-22. doi: 10.1097/00006454-199902000-00007.

    PubMed 10048682
  • Noah TL, Becker S. Respiratory syncytial virus-induced cytokine production by a human bronchial epithelial cell line. Am J Physiol. 1993 Nov;265(5 Pt 1):L472-8. doi: 10.1152/ajplung.1993.265.5.L472.

    PubMed 8238534
  • Garofalo R, Kimpen JL, Welliver RC, Ogra PL. Eosinophil degranulation in the respiratory tract during naturally acquired respiratory syncytial virus infection. J Pediatr. 1992 Jan;120(1):28-32. doi: 10.1016/s0022-3476(05)80592-x.

    PubMed 1731020
  • Volovitz B, Faden H, Ogra PL. Release of leukotriene C4 in respiratory tract during acute viral infection. J Pediatr. 1988 Feb;112(2):218-22. doi: 10.1016/s0022-3476(88)80058-1.

    PubMed 3339502

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Dexamethasone orally., Dexamethasone parenteral. and Inhaled nebulized Budesonide. in people with Bronchiolitis; Respiratory Syncytial Virus, run by Assiut University.

The full registered description is in the About this study section and the official record.

Who may be eligible to take part?

The sponsor lists 6 inclusion and 12 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.

Is this clinical trial currently recruiting?

The record says: status not confirmed, as of the sponsor's last update on 9 Jan 2019. Status can change between updates, so confirm with the study contact before making plans.

What are the possible benefits and risks?

They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.

What does this phase mean?

Phase 1 studies test a treatment in a small group of people for the first time or in a new way, mainly to check safety and find the right dose.

Not every study follows the same path, and some studies (observational studies, device studies) have no phase.

Are results available for this study?

Results are not available in the source record.

How can a doctor refer a patient or contact the research team?

The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.

What does the primary outcome measure?

Resolution of respiratory distress. (time frame: <7 days). It is what the study was designed to measure, not a finding.

Where can I read the original study information?

On the ClinicalTrials.gov record for NCT03436225, which also lists 25 linked publications.

Does a listing mean the treatment is approved or proven to work?

No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.

How often is this information updated?

AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 9 Jan 2019.

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