EFFECT OF AEROSOLIZED RECOMBINANT HUMAN DNase ON EXACERBATIONS OF RESPIRATORY SYMPTOMS AND ON PULMONARY FUNCTION IN PATIENTS WITH CYSTIC FIBROSIS

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Fuchs HJ, et al. "Effect of aerosolized recombinant human DNase on exacerbations of respiratory symptoms and on pulmonary function in patients with cystic fibrosis. The Pulmozyme Study Group". New England Journal of Medicine. 1994. 331(10):637-642.
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Clinical Question

Bottom Line

Major Points

Several small and large randomized trials in diabetics had previously suggested a sizable benefit of tight glycemic control in reducing cardiovascular risk. The ACCORD trial was the largest study of its kind and demonstrated that not only does euglycemia (ie, HbA1c <6%) not reduce cardiovascular risk, it also is associated with a trend towards increased mortality.

Guidelines

Design

  • Multicenter,randomized, placebo-controlled trial over 24 weeks
  • N=968
    • Daily (n=322)
    • Twice Daily (n=321)
    • Placebo (n=325)
  • Setting: 51 centers
  • Enrollment: Not described
  • Mean follow-up: N/A
  • Analysis: Intention-to-treat
  • Primary outcome: Maintain improvement in FEV1 and reduce the risk of pulmonary exacerbations requiring parenteral antibiotics

Population

Inclusion Criteria

  • Diagnosis of Cystic Fibrosis - sweat chloride > 60 mmol/L)
  • Forced Vital Capacity (FVC) > 40% predicted
  • Age [[>]] 5
  • Clinically Stable: receiving baseline regimen of antibiotics or no antimicrobial therapy 14 days prior to randomization

Exclusion Criteria

  • None Listed

Baseline Characteristics

  • Mean age: 72 years
  • Mean BMI: 28
  • Mean HbA1c: 8.8%
  • Units of insulin: 14 units/day

Interventions

  • Randomized to intensive (targeting HbA1c <6%) or standard (HbA1c 7-7.9%) glycemic therapy

    • Then 46% were randomized to intensive (SBP <120) vs. standard (SBP <140) blood pressure therapy
    • Remaining 54% randomized to fenofibrate vs. placebo; all received statin
  • Intensive glycemic control group attended monthly visits for 4 months, then every 2 months, with additional visits and telephone calls as needed
  • Standard therapy group had glycemic control visits every 4 months

Outcomes

Comparisons are intensive therapy vs. standard therapy.

Primary Outcomes

PRIMARY OUTCOME
##% vs. ##% (HR ##; 95% CI ##-##; P=##)

Secondary Outcomes

Subgroup Analysis

Adverse Events

Criticisms

Funding

Further Reading