NCT02960503

Brief Summary

Sickle cell anemia (SCA) is a life-threatening, monogenic disorder associated with early death when compared to individuals without SCA. Pulmonary complications, namely acute chest syndrome, obstructive lung disease and pulmonary hypertension, are the most common causes of death in patients with SCA. Recent studies suggest that lung specific inflammation is a hallmark of SCA and underlies pulmonary pathology. To date, no therapy has been shown to improve the pulmonary complications of SCA. Macrolides have pleomorphic effects in the lung with improvement in pulmonary function, symptoms and inflammatory markers demonstrated in several inflammatory pulmonary conditions such as cystic fibrosis, asthma, COPD and post-transplant bronchiolitis obliterans. Investigators hypothesize that low dose macrolide therapy is well tolerated and can improve pulmonary function and symptoms in patients with SCA. The objective of this project is to assess the feasibility of macrolides to attenuate or reverse the decrease in %predicted FEV1 in adults with SCA in a single-site, randomized, placebo-controlled feasibility trial.

Trial Health

30
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Sep 2016

Typical duration for phase_1

Geographic Reach
1 country

1 active site

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

Study Start

First participant enrolled

September 1, 2016

Completed
2 months until next milestone

First Submitted

Initial submission to the registry

November 2, 2016

Completed
7 days until next milestone

First Posted

Study publicly available on registry

November 9, 2016

Completed
1.9 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

October 1, 2018

Completed
Same day until next milestone

Study Completion

Last participant's last visit for all outcomes

October 1, 2018

Completed
Last Updated

October 2, 2018

Status Verified

September 1, 2018

Enrollment Period

2.1 years

First QC Date

November 2, 2016

Last Update Submit

September 28, 2018

Conditions

Sickle Cell Disease

Keywords

sickle cell diseasepulmonary complicationsreduced FEV1azithromycinlung function

Outcome Measures

Primary Outcomes (1)

  • Acceptability of the trial will be assessed by the modified Morisky Medication Adherence Scale (MMAS - 8)

    Acceptability of the trial will be measured based on three outcomes: recruitment, retention, and adherence rates to therapy. Retention defined as the number of participants that complete the entire study. Recruitment defined as the number of eligible participants that elect to consent to continue with study evaluations. Adherence rate measured based on MMAS score, which was previously validated in children with sickle cell disease (SCD) and scored as follows: high adherence (8 points), average adherence (6 to 7 points) and poor adherence (0 - 5 points).

    6 months

Secondary Outcomes (4)

  • Change in FEV1 % predicted in response to 6 months of low dose azithromycin therapy

    6 months

  • Change in respiratory symptom score (by ATS-DLD-78) in response to 6 months of low dose azithromycin therapy

    6 months

  • Change in quality of life (by SF-36) in response to 6 months of low dose azithromycin therapy

    6 months

  • Number of participants with treatment-related adverse events

    6 months

Study Arms (2)

Treatment arm (azithromycin)

ACTIVE COMPARATOR

Treatment arm: azithromycin 500 mg three times a week for 6 months

Drug: Azithromycin

Placebo arm

PLACEBO COMPARATOR

Control arm: placebo three times a week for 6 months

Other: Placebo

Interventions

AzithromycinDRUG

Study participants will be randomized to the treatment arm (azithromycin 500 mg three times a week for 6 months).

Also known as: Zithromax, zmax, z-pack
Treatment arm (azithromycin)
PlaceboOTHER

Study participants will be randomized to the control arm (placebo three times a week for 6 months).

Placebo arm

Eligibility Criteria

Age18 Years - 50 Years
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64)

You may qualify if:

  • Established diagnosis of sickle cell disease (HbSS, HbSC, HbS/β+, HbS/β0)
  • Age between 18-50 years
  • FEV1 \< 80% predicted
  • Willingness to make return visits and availability by telephone for the duration of the study.

You may not qualify if:

  • Acute respiratory symptoms
  • FEV1\>80%
  • Inability to swallow pills
  • Hypersensitivity to macrolides.
  • History of cardiac arrhythmias
  • Prolonged QTc interval (\>500 ms) at on baseline EKG
  • Baseline impairment of hearing by pure tone audiometry defined as patients with age-adjusted hearing thresholds \>95th percentile at any one frequency of 500, 1000, 2000 and 4000 Hz.
  • The presence of a diagnosis other than SCD that results in the patient being medically unstable, or having a predicted life expectancy less than 1 year.
  • Special patient groups: prisoners, pregnant women, institutionalized patients
  • Women who are at risk of becoming pregnant during the study, and who refuse to use an acceptable means of birth control (hormonal based oral, intrauterine device or barrier contraception) for the duration of the study.
  • Patients taking tacrolimus, pimozide, disopyramide, cyclosporine, nelfinavir, bromocriptine, or hexobarbital.
  • Patients taking any medications that prolong QTc interval.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (1)

Vanderbilt University Medical Center

Nashville, Tennessee, 37203, United States

Location

Related Publications (10)

  • Platt OS, Brambilla DJ, Rosse WF, Milner PF, Castro O, Steinberg MH, Klug PP. Mortality in sickle cell disease. Life expectancy and risk factors for early death. N Engl J Med. 1994 Jun 9;330(23):1639-44. doi: 10.1056/NEJM199406093302303.

    PMID: 7993409BACKGROUND

  • Bunn HF. Pathogenesis and treatment of sickle cell disease. N Engl J Med. 1997 Sep 11;337(11):762-9. doi: 10.1056/NEJM199709113371107. No abstract available.

    PMID: 9287233BACKGROUND

  • 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: 10861320BACKGROUND

  • Gladwin MT, Sachdev V, Jison ML, Shizukuda Y, Plehn JF, Minter K, Brown B, Coles WA, Nichols JS, Ernst I, Hunter LA, Blackwelder WC, Schechter AN, Rodgers GP, Castro O, Ognibene FP. Pulmonary hypertension as a risk factor for death in patients with sickle cell disease. N Engl J Med. 2004 Feb 26;350(9):886-95. doi: 10.1056/NEJMoa035477.

    PMID: 14985486BACKGROUND

  • Machado RF, Hildesheim M, Mendelsohn L, Remaley AT, Kato GJ, Gladwin MT. NT-pro brain natriuretic peptide levels and the risk of death in the cooperative study of sickle cell disease. Br J Haematol. 2011 Aug;154(4):512-20. doi: 10.1111/j.1365-2141.2011.08777.x. Epub 2011 Jun 21.

    PMID: 21689089BACKGROUND

  • Boyd JH, Macklin EA, Strunk RC, DeBaun MR. Asthma is associated with increased mortality in individuals with sickle cell anemia. Haematologica. 2007 Aug;92(8):1115-8. doi: 10.3324/haematol.11213.

    PMID: 17650441BACKGROUND

  • Field JJ, DeBaun MR. Asthma and sickle cell disease: two distinct diseases or part of the same process? Hematology Am Soc Hematol Educ Program. 2009:45-53. doi: 10.1182/asheducation-2009.1.45.

    PMID: 20008181BACKGROUND

  • Kassim AA, Payne AB, Rodeghier M, Macklin EA, Strunk RC, DeBaun MR. Low forced expiratory volume is associated with earlier death in sickle cell anemia. Blood. 2015 Sep 24;126(13):1544-50. doi: 10.1182/blood-2015-05-644435. Epub 2015 Aug 10.

    PMID: 26261241BACKGROUND

  • Quanjer PH, Stanojevic S, Cole TJ, Baur X, Hall GL, Culver BH, Enright PL, Hankinson JL, Ip MS, Zheng J, Stocks J; ERS Global Lung Function Initiative. Multi-ethnic reference values for spirometry for the 3-95-yr age range: the global lung function 2012 equations. Eur Respir J. 2012 Dec;40(6):1324-43. doi: 10.1183/09031936.00080312. Epub 2012 Jun 27.

    PMID: 22743675BACKGROUND

  • Bakheit AH, Al-Hadiya BM, Abd-Elgalil AA. Azithromycin. Profiles Drug Subst Excip Relat Methodol. 2014;39:1-40. doi: 10.1016/B978-0-12-800173-8.00001-5.

    PMID: 24794904BACKGROUND

MeSH Terms

Conditions

Anemia, Sickle Cell

Interventions

Azithromycin

Condition Hierarchy (Ancestors)

Anemia, Hemolytic, CongenitalAnemia, HemolyticAnemiaHematologic DiseasesHemic and Lymphatic DiseasesHemoglobinopathiesGenetic Diseases, InbornCongenital, Hereditary, and Neonatal Diseases and Abnormalities

Intervention Hierarchy (Ancestors)

ErythromycinMacrolidesPolyketidesLactonesOrganic Chemicals

Study Officials

  • Michael R. DeBaun, M.D., M.P.H.

    Vanderbilt University Medical Center

    PRINCIPAL INVESTIGATOR
0

Study Design

Study Type
interventional
Phase
phase 1
Allocation
RANDOMIZED
Masking
QUADRUPLE
Who Masked
PARTICIPANT, CARE PROVIDER, INVESTIGATOR, OUTCOMES ASSESSOR
Purpose
OTHER
Intervention Model
PARALLEL
Sponsor Type
OTHER
Responsible Party
PRINCIPAL INVESTIGATOR
PI Title
Professor of Pediatrics and Medicine, Vice Chair for Clinical and Translational Research, J.C. Peterson Chair in Pediatric Pulmonology, Director, Vanderbilt-Meharry Center for Excellence in Sickle Cell Disease

Study Record Dates

First Submitted

November 2, 2016

First Posted

November 9, 2016

Study Start

September 1, 2016

Primary Completion

October 1, 2018

Study Completion

October 1, 2018

Last Updated

October 2, 2018

Record last verified: 2018-09

Data Sharing

IPD Sharing
Will share

Locations

US(1)