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Sickle Cell DiseasePhase 1NCT02630394

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

A Phase 1 study testing Azithromycin in people with Sickle Cell Disease and Acute Chest Syndrome, run by University of Mississippi Medical Center at 2 sites in United States.

Withdrawn

Withdrawn. The study stopped before anyone enrolled.

Official record
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Trial 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. Read more about this study

Who is it for?
Ages 6 to 16 years
Conditions the study is for
Sickle Cell Disease, Acute Chest Syndrome
What is being tested?
Azithromycin
Type of treatment
Pill or oral medicine
Could I receive a placebo?
No, everyone receives an active treatment
How many people
0 participants
Where
2 sitesUnited States
Study dates
Sep 2015to 31 Dec 2017
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 6 to 16 years
  • All sexes
  • No healthy volunteers
  • Child

Who may be able to join

  • 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

Who cannot join

  • 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
Show all 10Show fewer
  • Chronic red blood cell transfusion
  • History of allergy to azithromycin or macrolide antibiotic
  • History of cardiac arrhythmia
  • History of prolonged QT

Trial locations and contacts

2 sites in 1 country.

United States2 sites
  • University of Mississippi Medical Center

    Jackson, Mississippi, 39216

  • Vanderbilt University

    Nashville, Tennessee

Other trials in United States

About this study

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.

Read the detailed description

Specific Aims:

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. Recurrent ACS has been associated with poor lung function outcome that is comparable to cystic fibrosis. 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. Thus newer therapies are urgently needed to address this important issue associated with increased morbidity from debilitating chronic lung disease and mortality in SCD. Macrolides are a group of antibiotics that exert immunomodulatory and anti-inflammatory actions both in vitro and in vivo. It has been shown to inhibit neutrophil activation and mobilization, modulate oxidant production by neutrophils and of proinflammatory cytokine synthesis and release by leukocytes, reduce systemic markers of inflammation, inhibit intercellular adhesion molecules on epithelial cell surfaces, and block the activation of certain nuclear transcription factors. In addition, macrolides reduce bacterial burden in the airway of atypical organisms, all of which play an important role in the pathophysiology of ACS. Indeed, 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. However, azithromycin has never been studied before in SCD. 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 following specific aims:

Specific Aim 1: Examine the feasibility, safety and tolerability of azithromycin prophylaxis administration in children with SCD. A cohort of 15 participants with sickle cell disease 6 to 16 years old will be placed on azithromycin prophylaxis, and followed closely to evaluate medication adherence and for any adverse effects from taking the medication.

Specific Aim 2: Examine whether azithromycin prophylaxis has the potential to improve lung outcome in participants with SCD with a history of ACS. In the same cohort of 15 patients, baseline pulmonary function testing will be performed evaluating Forced expiratory volume 1 sec (FEV1) and Forced vital capacity (FVC) measurements prior to starting azithromycin prophylaxis, and then again at study end period after 1 year to evaluate for any change.

Specific Aim 3: Determine whether azithromycin prophylaxis reduces inflammation in participants with SCD with a history of ACS. In the same cohort of 15 participants, baseline markers of inflammation will be performed, specifically C-reactive protein (CRP), Tumor necrosis factor Alpha (TNF-α), interleukin IL-1, IL-1β, IL-4, IL-6, and IL-8, and then repeated at specific time intervals of 16 weeks, 32 weeks and 48 weeks (study end).

Being tested
Azithromycin
Keywords
sickle cell disease, acute chest syndrome
Medical subject headings
Anemia, Sickle Cell, Acute Chest Syndrome

What participants receive

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

Study groups in NCT02630394
Study groupRoleWhat they receive
Azithromycin prophylaxisExperimentalAzithromycin 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.
Receives: Drug: Azithromycin

What is being measured

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

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

    Measured: 48 weeks

Secondary outcomes (3)
  1. Percent adherence with azithromycin prophylaxis

    Measured: 48 weeks

  2. Number of participants with improved forced vital capacity (cm3)

    Measured: 48 weeks

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

    Measured: 48 weeks

Timeline

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

  1. First posted15 Dec 2015 (estimated)
  2. Study startSep 2015
  3. Primary completion31 Dec 2017 (estimated)
  4. Study completion31 Dec 2017

Why it stopped: Principal Investigator has moved to another institution

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
Prevention
Allocation
Not applicable
Intervention model
Single group
Masking
None (open label)
Enrolment
0 participants (actual)
IDs, dates and publications
ClinicalTrials.gov ID
NCT02630394
Sponsor's protocol ID
SCD_ACS_AZM
Status last verified
Jun 2018
First submitted
26 Nov 2015
Last updated
21 Jun 2018
Results posted
No
Data monitoring committee
Yes

Publications

  • 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.

    PubMed 7517723
  • 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.

    PubMed 10861320
  • 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.

    PubMed 12544773
  • 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.

    PubMed 16690969
  • 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.

    PubMed 15741436
  • 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.

    PubMed 25619382
  • 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.

    PubMed 22105373
  • 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.

    PubMed 14519709
  • 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.

    PubMed 22595153

Questions about this trial

What is this clinical trial studying?

A Phase 1 study testing Azithromycin in people with Sickle Cell Disease and Acute Chest Syndrome, run by University of Mississippi Medical Center at 2 sites in United States.

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 3 inclusion and 10 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: withdrawn, as of the sponsor's last update on 21 Jun 2018. Status can change between updates, so confirm with the study contact before making plans.

Where is the study taking place?

The record lists 2 sites in United States. Whether a site is taking part right now should be confirmed with that site. See every site.

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?

The study was withdrawn before enrolling participants, so there are no results.

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?

Number of participants with treatment-related adverse events as assessed by CTCAE v4.0 (time frame: 48 weeks). 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 NCT02630394, which also lists 9 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 21 Jun 2018.

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