History of NHLBI Clinical Research Networks
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Transcript of History of NHLBI Clinical Research Networks
History of NHLBI Clinical Research Networks
Adult Asthma
Acute Respiratory Distress Syndrome
Childhood Asthma
Thalassemia
Pediatric Heart Disease
Blood and Marrow Transplant
Transfusion Medicine Hemostasis
COPD
Pulmonary Fibrosis
Sickle Cell Disease
Heart Failure
Resuscitation Outcomes Consortium
Cardiovascular Cell Therapy
Cardiothoracic Surgical Investigations
AsthmaNet
AsthmaNet Mission Statement
• The mission of AsthmaNet is to break new ground by providing evidence which enables advances in asthma treatment that will have high impact on patient management through clinical trials that seek to fill gaps in knowledge, to personalize asthma therapy, and to identify new therapies.
• The unification of prior NIH investment in separate pediatric and adult networks into one AsthmaNet will enhance scientific exchange and stimulate research that addresses questions about the similarities, differences, and relationships between childhood and adult asthma.
• AsthmaNet will provide experience and opportunities to develop new investigators.
AsthmaNet Approach
• AsthmaNet protocols will include large-scale Clinical Management trials to carefully evaluate existing or new therapeutic approaches to asthma management. These protocols may be accompanied by mechanistic studies.
• Proof-of-concept studies also will be conducted to identify promising agents or approaches to asthma therapy which might be considered for subsequent larger scale testing.
• Over the 7-year project period, we will conduct 6-8 Clinical Management trials– at least 3 protocols focused on questions in adult patients– at least 3 protocols directed towards pediatric patients
at least 1 across-the-lifetime trial– One or two of these trials may be long-term preventative trials– 4-6 Proof of Concept studies
NHLBI
PRC DSMB
Steering Committee
DCC
Clinical Sites
Internal Committees
Regulatory Agencies
NIH AsthmaNet
AsthmaNet Protocol TimelinesAsthmaNet Protocol Timelines
• To provide junior clinical investigators with outstanding opportunity to refine their research skills through:– One-on-one mentoring– Participation in AsthmaNet activities– Preparation of ancillary protocols– Involvement in conduct of clinical trials
Clinical Research Skills Development Core
Vitamin D add-on therapy enhances corticosteroid responsiveness in Asthma
(VIDA)
10
• Significant variability in response to inhaled corticosteroids (ICS) has been reported
• Optimal asthma control is often not achieved with ICS, necessitating add-on therapy
• Emerging data suggest vitamin D may modulate asthma phenotypes, among them glucocorticoid response
Protocol Pg 6-12
Rationale
Vitamin D Deficiency & Asthma
• CAMP participants with Vit D insufficiency had ↓lung function and ↑risk for exacerbations
• Children: increase in Vit D levels associated with reduced: – hospitalization– anti-inflammatory medications– airway hyperresponsiveness
• Adults: Vit D insufficient (<30 ng/mL) subjects demonstrate:– increased airway hyperresponsiveness– decreased lung function– decreased steroid response in vitro
Protocol Pg 6-12
• In individuals 18 years and older with persistent asthma who remain symptomatic despite low dose ICS and who are vitamin D insufficient (<30 ng/ml), the addition of vitamin D is superior to placebo in reducing treatment failures
Primary Hypothesis
Protocol Pg 13
VIDA Study Design (n=400 adults)
Protocol Pg 19
•Population: adults with asthma and vitamin D insufficiency (<30 ng/mL)•Intervention: vitamin D or placebo added to low-dose ICS•Primary outcome: post-randomization treatment failure•Secondary outcomes: multiple
APRIL - Azithromycin for Preventing the development of upper Respiratory tract
Illness into Lower respiratory tract symptoms in children
And
OCELOT - Oral Corticosteroids for treating Episodes of significant LOwer respiratory
Tract symptoms in children
• Severe episodes of lower respiratory tract symptoms are common in early childhood
• Disproportionate amount of health-care resources used in this age group
• Little evidence to guide practitioners for episode prevention
• Controversy as to the efficacy of oral corticosteroids at decreasing symptom burden during severe wheezing episodes
Background
Overview
SYMPTOMS
Onset of RTI symptoms
Is azithromycin more effective than placebo for
preventing clinically significant LRT symptoms?
APRIL Treatment Failure: Progression of LRT Symptoms
Does the addition of oral corticosteroids during an acute episode reduce the
severity of the episode?
APRILOCELOT
2 separate but linked trials conducted in 600 children 12-71 months of age with a history of a clinically significant wheezing in the prior year
• 2 separate and unique interventions at differing stages of RTI progression
• Factorial design• Maximizes trial efficiency
Recruitment of a single “cohort” of children Two trials that function independently
o Participation in OCELOT once APRIL treatment failure is achieved (and thus APRIL participation is complete)
Two Separate But Linked Trials
Co-Primary HypothesesCo-PRIMARY HYPOTHESES: Among preschool-aged children with recurrent wheezing episodes and one or more clinically significant wheezing episode in the year prior to enrollment:
1. The risk of progression to clinically significant lower respiratory tract symptoms is lower if azithromycin is given at the early signs of an RTI compared with placebo. (APRIL - Prevention Trial)
2. The severity of clinically significant lower respiratory tract symptoms is lower if oral corticosteroids are given for rescue due to symptom progression compared with placebo. (OCELOT - Treatment Trial)
Treatment Strategies
SYMPTOMS
Onset of RTI symptoms
Begin APRIL Illness Kit:
Azithromycin or Placebo
APRIL Treatment Failure (APRIL Primary Outcome): Progression
of Symptoms
Begin OCELOT Rescue Kit:
Prednisolone or Placebo
See Child within 36-72 hrs in Center
Clinic & assess PRAM (OCELOT Primary
Outcome)
APRIL OCELOT
Clinical Care per Physician Discretion