A Pilot Study of Azithromycin Prophylaxis for Acute Chest Syndrome in Sickle Cell Disease

NCT02630394 | Withdrawn Phase 1 DMC

• 1 other identifier: SCD_ACS_AZM
• Study Type: interventional
• Target: N/A
• Locations: 1 country
• Sites: 2

Brief Summary

Acute chest syndrome (ACS), a lung complication in sickle cell disease (SCD), is the second most common cause of hospitalization and leading cause of death in SCD. ACS is associated with airway inflammation, and a major cause is pulmonary infection from atypical organisms. To date, there are no drugs available to reduce inflammation and risk of recurrent ACS. Macrolides are a group of antibiotics that exert immunomodulatory and anti-inflammatory actions both in vitro and in vivo. In addition, macrolides reduce bacterial burden in the airway of atypical organisms, all of which play an important role in the pathophysiology of ACS. Numerous studies have evaluated macrolide prophylaxis in conditions associated with lung inflammation, such as cystic fibrosis, asthma, bronchiectasis etc., and high quality evidence have found macrolides to be beneficial as a disease modifying agent that leads to improvement in airway inflammation, reduced pulmonary exacerbations and improved lung function. The investigators hypothesize that azithromycin prophylaxis is well tolerated and has the potential to reduce inflammation and improve lung outcome in children with SCD with a history of ACS. A prospective, single arm, open label feasibility study of azithromycin prophylaxis will be performed in children with SCD with a history ACS with the specific aim to examine the feasibility, safety and tolerability of azithromycin prophylaxis administration in participants with SCD , and to examine whether azithromycin prophylaxis has the potential to improve lung outcome. In addition, this study will determine whether azithromycin prophylaxis reduces inflammation in participants with SCD with a history of ACS.

Conditions

Sickle Cell Disease; Acute Chest Syndrome

Keywords

sickle cell disease; acute chest syndrome

Outcome Measures

Primary Outcomes (1)

• Number of participants with treatment-related adverse events as assessed by CTCAE v4.0

  48 weeks

Secondary Outcomes (3)

• Percent adherence with azithromycin prophylaxis

  48 weeks

• Number of participants with improved forced vital capacity (cm3)

  48 weeks

• Number of participants with improved forced expiratory volume 1 (cm3/sec)

  48 weeks

Study Arms (1)

Azithromycin prophylaxis

EXPERIMENTAL

Azithromycin will be supplied as a 250-mg tablet. Participants weighing less than 40 mg will be instructed to take 1 tablet 3 days a week (Monday, Wednesday, and Friday), and participants who weigh more than 40 kg will be instructed to take 2 tablets on the same 3 days per week.

Drug: Azithromycin

Interventions

Azithromycin DRUG

Also known as: Zithromax

Azithromycin prophylaxis

Eligibility Criteria

• Age: 6 Years - 16 Years
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17)

You may qualify if:

• Established diagnosis of SCD (Hemoglobin SS, hemoglobin Sβ0 thalassemia)
• History of acute chest syndrome - the history of acute chest syndrome will be confirmed by a retrospective medical chart review that meets the standard definition as mentioned in the Background section.
• Age ≥ 6 years to 16 years old

You may not qualify if:

• Hemoglobin Sβ+thalassemia and hemoglobin SC subject will be excluded as this group of patients do not typically have severe SCD that places them at risk of developing recurrent acute chest syndrome
• No history of acute chest syndrome
• Significant neurologic impairment as judged by health care provider.
• Inability to take/swallow a tablet
• History of poor adherence to clinic visits.
• History of renal or hepatic dysfunction
• Chronic red blood cell transfusion
• History of allergy to azithromycin or macrolide antibiotic
• History of cardiac arrhythmia
• History of prolonged QT

Sponsors & Collaborators

• University of Mississippi Medical Center: lead

Study Sites (2)

University of Mississippi Medical Center

Jackson, Mississippi, 39216, United States

Location

Vanderbilt University

Nashville, Tennessee, United States

Location

Related Publications (9)

• Castro O, Brambilla DJ, Thorington B, Reindorf CA, Scott RB, Gillette P, Vera JC, Levy PS. The acute chest syndrome in sickle cell disease: incidence and risk factors. The Cooperative Study of Sickle Cell Disease. Blood. 1994 Jul 15;84(2):643-9.

  PMID: 7517723 BACKGROUND

• Vichinsky EP, Neumayr LD, Earles AN, Williams R, Lennette ET, Dean D, Nickerson B, Orringer E, McKie V, Bellevue R, Daeschner C, Manci EA. Causes and outcomes of the acute chest syndrome in sickle cell disease. National Acute Chest Syndrome Study Group. N Engl J Med. 2000 Jun 22;342(25):1855-65. doi: 10.1056/NEJM200006223422502.

  PMID: 10861320 BACKGROUND

• Dean D, Neumayr L, Kelly DM, Ballas SK, Kleman K, Robertson S, Iyer RV, Ware RE, Koshy M, Rackoff WR, Pegelow CH, Waldron P, Benjamin L, Vichinsky E; Acute Chest Syndrome Study Group. Chlamydia pneumoniae and acute chest syndrome in patients with sickle cell disease. J Pediatr Hematol Oncol. 2003 Jan;25(1):46-55. doi: 10.1097/00043426-200301000-00010.

  PMID: 12544773 BACKGROUND

• Boyd JH, Macklin EA, Strunk RC, DeBaun MR. Asthma is associated with acute chest syndrome and pain in children with sickle cell anemia. Blood. 2006 Nov 1;108(9):2923-7. doi: 10.1182/blood-2006-01-011072. Epub 2006 May 11.

  PMID: 16690969 BACKGROUND

• Knight-Madden JM, Forrester TS, Lewis NA, Greenough A. Asthma in children with sickle cell disease and its association with acute chest syndrome. Thorax. 2005 Mar;60(3):206-10. doi: 10.1136/thx.2004.029165.

  PMID: 15741436 BACKGROUND

• Vance LD, Rodeghier M, Cohen RT, Rosen CL, Kirkham FJ, Strunk RC, DeBaun MR. Increased risk of severe vaso-occlusive episodes after initial acute chest syndrome in children with sickle cell anemia less than 4 years old: Sleep and asthma cohort. Am J Hematol. 2015 May;90(5):371-5. doi: 10.1002/ajh.23959. Epub 2015 Mar 30.

  PMID: 25619382 BACKGROUND

• Zarogoulidis P, Papanas N, Kioumis I, Chatzaki E, Maltezos E, Zarogoulidis K. Macrolides: from in vitro anti-inflammatory and immunomodulatory properties to clinical practice in respiratory diseases. Eur J Clin Pharmacol. 2012 May;68(5):479-503. doi: 10.1007/s00228-011-1161-x. Epub 2011 Nov 22.

  PMID: 22105373 BACKGROUND

• Saiman L, Marshall BC, Mayer-Hamblett N, Burns JL, Quittner AL, Cibene DA, Coquillette S, Fieberg AY, Accurso FJ, Campbell PW 3rd; Macrolide Study Group. Azithromycin in patients with cystic fibrosis chronically infected with Pseudomonas aeruginosa: a randomized controlled trial. JAMA. 2003 Oct 1;290(13):1749-56. doi: 10.1001/jama.290.13.1749.

  PMID: 14519709 BACKGROUND

• Ratjen F, Saiman L, Mayer-Hamblett N, Lands LC, Kloster M, Thompson V, Emmett P, Marshall B, Accurso F, Sagel S, Anstead M. Effect of azithromycin on systemic markers of inflammation in patients with cystic fibrosis uninfected with Pseudomonas aeruginosa. Chest. 2012 Nov;142(5):1259-1266. doi: 10.1378/chest.12-0628.

  PMID: 22595153 BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell; Acute Chest Syndrome

Interventions

Azithromycin

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; Lung Diseases; Respiratory Tract Diseases; Respiration Disorders

Intervention Hierarchy (Ancestors)

Erythromycin; Macrolides; Polyketides; Lactones; Organic Chemicals

Study Design

• Study Type: interventional
• Phase: phase 1
• Allocation: NA
• Masking: NONE
• Purpose: PREVENTION
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Associate Professor of Pediatrics

Study Record Dates

• First Submitted: November 26, 2015
• First Posted: December 15, 2015
• Study Start: September 1, 2015
• Primary Completion: December 31, 2017
• Study Completion: December 31, 2017
• Last Updated: June 21, 2018

Record last verified: 2018-06

Locations

US (2)