Dataset Information

Oral antimycobacterial therapy in chronic cutaneous sarcoidosis: a randomized, single-masked, placebo-controlled study.

ABSTRACT:

Importance

Sarcoidosis is a chronic granulomatous disease for which there are limited therapeutic options. This is the first randomized, placebo-controlled study to demonstrate that antimycobacterial therapy reduces lesion diameter and disease severity among patients with chronic cutaneous sarcoidosis.

Objective

To evaluate the safety and efficacy of once-daily antimycobacterial therapy on the resolution of chronic cutaneous sarcoidosis lesions.

Design and participants

A randomized, placebo-controlled, single-masked trial on 30 patients with symptomatic chronic cutaneous sarcoidosis lesions deemed to require therapeutic intervention.

Setting

A tertiary referral dermatology center in Nashville, Tennessee.

Interventions

Participants were randomized to receive either the oral concomitant levofloxacin, ethambutol, azithromycin, and rifampin (CLEAR) regimen or a comparative placebo regimen for 8 weeks with a 180-day follow-up.

Main outcomes and measures

Participants were monitored for absolute change in lesion diameter and decrease in granuloma burden, if present, on completion of therapy.

Observations

In the intention-to-treat analysis, the CLEAR-treated group had a mean (SD) decrease in lesion diameter of -8.4 (14.0) mm compared with an increase of 0.07 (3.2) mm in the placebo-treated group (P = .05). The CLEAR group had a significant reduction in granuloma burden and experienced a mean (SD) decline of -2.9 (2.5) mm in lesion severity compared with a decline of -0.6 (2.1) mm in the placebo group (P = .02).

Conclusions and relevance

Antimycobacterial therapy may result in significant reductions in chronic cutaneous sarcoidosis lesion diameter compared with placebo. These observed reductions, associated with a clinically significant improvement in symptoms, were present at the 180-day follow-up period. Transcriptome analysis of sarcoidosis CD4+ T cells revealed reversal of pathways associated with disease severity and enhanced T-cell function following T-cell receptor stimulation.

Trial registration

clinicaltrials.gov Identifier: NCT01074554.

SUBMITTER: Drake WP

PROVIDER: S-EPMC3927541 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

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Publications

Oral antimycobacterial therapy in chronic cutaneous sarcoidosis: a randomized, single-masked, placebo-controlled study.

Drake Wonder P WP Oswald-Richter Kyra K Richmond Bradley W BW Isom Joan J Burke Victoria E VE Algood Holly H Braun Nicole N Taylor Thyneice T Pandit Kusum V KV Aboud Caroline C Yu Chang C Kaminski Naftali N Boyd Alan S AS King Lloyd E LE

JAMA dermatology 20130901 9

<h4>Importance</h4>Sarcoidosis is a chronic granulomatous disease for which there are limited therapeutic options. This is the first randomized, placebo-controlled study to demonstrate that antimycobacterial therapy reduces lesion diameter and disease severity among patients with chronic cutaneous sarcoidosis.<h4>Objective</h4>To evaluate the safety and efficacy of once-daily antimycobacterial therapy on the resolution of chronic cutaneous sarcoidosis lesions.<h4>Design and participants</h4>A ra ...[more]

PMID: 23863960

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Project description:BackgroundA Phase I, single-center investigation found that 8 weeks of antimycobacterial therapy improved sarcoidosis FVC. Safety and efficacy assessments have not been performed in a multicenter cohort.Research questionThe objective of this study was to determine the safety and efficacy of antimycobacterial therapy on the physiological and immunologic end points of sarcoidosis.Study design and methodsIn a double-blind, placebo-controlled, multicenter investigation, patients with pulmonary sarcoidosis were randomly assigned to receive 16 weeks of concomitant levofloxacin, ethambutol, azithromycin, and rifabutin (CLEAR) or matching placebo to investigate the effect on FVC. The primary outcome was a comparison of change in percentage of predicted FVC among patients randomized to receive CLEAR or placebo in addition to their baseline immunosuppressive regimen. Secondary outcomes included 6-min walk distance (6MWD), St. George's Respiratory Questionnaire (SGRQ) score, adverse events, and decrease in mycobacterial early secreted antigenic target of 6 kDa (ESAT-6) immune responses.ResultsThe intention-to-treat analysis revealed no significant differences in change in FVC among the 49 patients randomized to receive CLEAR (1.1% decrease) compared with the 48 randomized to receive placebo (0.02% increase) (P = .64). Physiological parameters such as the change in 6MWD were likewise similar (P = .91); change in SGRQ favored placebo (-8.0 for placebo vs -1.5 for CLEAR; P = .028). The per-protocol analysis revealed no significant change in FVC at 16 weeks between CLEAR and placebo. There was no significant change in 6MWD (36.4 m vs 6.3 m; P = .24) or SGRQ (-2.3 vs -7.0; P = .14). A decline in ESAT-6 immune responses at 16 weeks was noted among CLEAR-treated patients (P = .0003) but not patients receiving placebo (P = .24).InterpretationDespite a significant decline in ESAT-6 immune responses, a 16-week CLEAR regimen provided no physiological benefit in FVC or 6MWD among patients with sarcoidosis.

Project description:AimsMorphine is shown to relieve chronic breathlessness in chronic obstructive pulmonary disease. There are no definitive data in people with heart failure. We aimed to determine the effectiveness and cost-effectiveness of 12 weeks morphine therapy for the relief of chronic breathlessness in people with chronic heart failure compared with placebo.Methods and resultsParallel group, double-blind, randomized, placebo-controlled, phase III trial of 20 mg daily oral modified release morphine was conducted in 13 sites in England and Scotland: hospital/community cardiology or palliative care outpatients. The primary analysis compared between-group numerical rating scale average breathlessness/24 hours at week 4 using a covariance pattern linear mixed model. Secondary outcomes included treatment-emergent harms (worse or new). The trial closed early due to slow recruitment, randomizing 45 participants [average age 72 (range 39-89) years; 84% men; 98% New York Heart Association class III]. For the primary analysis, the adjusted mean difference was 0.26 (95% confidence interval, -0.86 to 1.37) in favour of placebo. All other breathlessness measures improved in both groups (week 4 change-from-baseline) but by more in those assigned to morphine. Neither group was excessively drowsy at baseline or week 4. There were no between-group differences in quality of life (Kansas) or cognition (Montreal) at any time point. There was no exercise-related desaturation and no change between baseline and week 4 in either group. There was no change in vital signs at week 4. The natriuretic peptide measures fell in both groups but by more in the morphine group [morphine 2169 (1092, 3851) pg/mL vs. placebo 2851 (1694, 5437)] pg/mL. There was no excess serious adverse events in the morphine group. Treatment-emergent harms during the first week were more common in the morphine group; all apart from 1 were ? grade 2.ConclusionsWe could not answer our primary objectives due to inadequate power. However, we provide novel placebo-controlled medium-term benefit and safety data useful for clinical practice and future trial design. Morphine should only be prescribed in this population when other measures are unhelpful and with early management of side effects.

Dataset Information

Oral antimycobacterial therapy in chronic cutaneous sarcoidosis: a randomized, single-masked, placebo-controlled study.

Importance

Objective

Design and participants

Setting

Interventions

Main outcomes and measures

Observations

Conclusions and relevance

Trial registration

Publications

Oral antimycobacterial therapy in chronic cutaneous sarcoidosis: a randomized, single-masked, placebo-controlled study.

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