Can We Make The In-Hospital LVAD Deactivation Process At End-of-life Comfortable?
HFSA ePoster Library. Singh M. 09/10/21; 343393; 167
Manavotam Singh
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Abstract
Discussion Forum (0)
Background: In planning and executing clinical trials, a key assumption involves change in the placebo group. Changes over time to an endpoint - such as natriuretic peptides (NP) - within a placebo group are a composite of the natural progression of disease, the variability in the measurement of the endpoint itself, and a placebo effect.
Methods: A systematic search of the MEDLINE database identified randomized controlled trials (RCTs) that evaluated drug or device effects on NP measurements (both brain natriuretic peptide (BNP) and N-terminal pro B-type Natriuretic Peptide (NT-proBNP)) in patients with heart failure (HF), for trials published between January 2015 and November 2020.
Results: From an abstract review of 334 studies from a MEDLINE search, with subsequent full text review, 27 double-blind placebo controlled RCTs were identified, with availability of either raw NP values or percentage change in NP values over the course of the trial. There were a total of 8,967 patients (69% male, average age 66 years) with HF (NYHA class I - 1%, class II - 54%, class III - 41%, class IV - 4 %) randomized to the placebo arm in the 27 studies. At trial completion (median duration 24 weeks, range 2 days to 106 weeks) the mean NP % change was - 6.5 +/- 31.2 %. Fourteen of 27 studies reported an NP decrease, and 13 reported an increase in NP values. Mean NP % change in trials of duration ≤ 24 weeks (n=15) was -12.4 +/- 29.1 %, whereas mean NP % change in trials > 24 weeks (n=12) was +4.5 +/- 32.5 % (p < 0.001 vs. ≤ 24 weeks).
Of the 27 RCTs, 4 trials included only patients with HF with preserved ejection fraction (HFpEF), 18 included only patients with HF with reduced ejection fraction (HFrEF), and 5 included both. The 4 trials with HFpEF patients had a total of 253 patients and had a mean NP % change of 9.0 +/- 28.4%. The 18 trials with HFrEF patients had a total of 7389 patients and had a mean NP % change of -1.3 +/- 27.0 % (p<0.001 vs. HFpEF)
Conclusion: In contemporary RCTs in patients with HF, NP responses in the placebo-group arm have wide variability, may increase or decrease, are different in patients with HFpEF or HFrEF, and are associated with the duration of the trial. The ability to quantify the contribution of placebo effects in the context of trial duration can help determine sample sizes and duration of study for trials involving biomarker endpoints.
Methods: A systematic search of the MEDLINE database identified randomized controlled trials (RCTs) that evaluated drug or device effects on NP measurements (both brain natriuretic peptide (BNP) and N-terminal pro B-type Natriuretic Peptide (NT-proBNP)) in patients with heart failure (HF), for trials published between January 2015 and November 2020.
Results: From an abstract review of 334 studies from a MEDLINE search, with subsequent full text review, 27 double-blind placebo controlled RCTs were identified, with availability of either raw NP values or percentage change in NP values over the course of the trial. There were a total of 8,967 patients (69% male, average age 66 years) with HF (NYHA class I - 1%, class II - 54%, class III - 41%, class IV - 4 %) randomized to the placebo arm in the 27 studies. At trial completion (median duration 24 weeks, range 2 days to 106 weeks) the mean NP % change was - 6.5 +/- 31.2 %. Fourteen of 27 studies reported an NP decrease, and 13 reported an increase in NP values. Mean NP % change in trials of duration ≤ 24 weeks (n=15) was -12.4 +/- 29.1 %, whereas mean NP % change in trials > 24 weeks (n=12) was +4.5 +/- 32.5 % (p < 0.001 vs. ≤ 24 weeks).
Of the 27 RCTs, 4 trials included only patients with HF with preserved ejection fraction (HFpEF), 18 included only patients with HF with reduced ejection fraction (HFrEF), and 5 included both. The 4 trials with HFpEF patients had a total of 253 patients and had a mean NP % change of 9.0 +/- 28.4%. The 18 trials with HFrEF patients had a total of 7389 patients and had a mean NP % change of -1.3 +/- 27.0 % (p<0.001 vs. HFpEF)
Conclusion: In contemporary RCTs in patients with HF, NP responses in the placebo-group arm have wide variability, may increase or decrease, are different in patients with HFpEF or HFrEF, and are associated with the duration of the trial. The ability to quantify the contribution of placebo effects in the context of trial duration can help determine sample sizes and duration of study for trials involving biomarker endpoints.
Background: In planning and executing clinical trials, a key assumption involves change in the placebo group. Changes over time to an endpoint - such as natriuretic peptides (NP) - within a placebo group are a composite of the natural progression of disease, the variability in the measurement of the endpoint itself, and a placebo effect.
Methods: A systematic search of the MEDLINE database identified randomized controlled trials (RCTs) that evaluated drug or device effects on NP measurements (both brain natriuretic peptide (BNP) and N-terminal pro B-type Natriuretic Peptide (NT-proBNP)) in patients with heart failure (HF), for trials published between January 2015 and November 2020.
Results: From an abstract review of 334 studies from a MEDLINE search, with subsequent full text review, 27 double-blind placebo controlled RCTs were identified, with availability of either raw NP values or percentage change in NP values over the course of the trial. There were a total of 8,967 patients (69% male, average age 66 years) with HF (NYHA class I - 1%, class II - 54%, class III - 41%, class IV - 4 %) randomized to the placebo arm in the 27 studies. At trial completion (median duration 24 weeks, range 2 days to 106 weeks) the mean NP % change was - 6.5 +/- 31.2 %. Fourteen of 27 studies reported an NP decrease, and 13 reported an increase in NP values. Mean NP % change in trials of duration ≤ 24 weeks (n=15) was -12.4 +/- 29.1 %, whereas mean NP % change in trials > 24 weeks (n=12) was +4.5 +/- 32.5 % (p < 0.001 vs. ≤ 24 weeks).
Of the 27 RCTs, 4 trials included only patients with HF with preserved ejection fraction (HFpEF), 18 included only patients with HF with reduced ejection fraction (HFrEF), and 5 included both. The 4 trials with HFpEF patients had a total of 253 patients and had a mean NP % change of 9.0 +/- 28.4%. The 18 trials with HFrEF patients had a total of 7389 patients and had a mean NP % change of -1.3 +/- 27.0 % (p<0.001 vs. HFpEF)
Conclusion: In contemporary RCTs in patients with HF, NP responses in the placebo-group arm have wide variability, may increase or decrease, are different in patients with HFpEF or HFrEF, and are associated with the duration of the trial. The ability to quantify the contribution of placebo effects in the context of trial duration can help determine sample sizes and duration of study for trials involving biomarker endpoints.
Methods: A systematic search of the MEDLINE database identified randomized controlled trials (RCTs) that evaluated drug or device effects on NP measurements (both brain natriuretic peptide (BNP) and N-terminal pro B-type Natriuretic Peptide (NT-proBNP)) in patients with heart failure (HF), for trials published between January 2015 and November 2020.
Results: From an abstract review of 334 studies from a MEDLINE search, with subsequent full text review, 27 double-blind placebo controlled RCTs were identified, with availability of either raw NP values or percentage change in NP values over the course of the trial. There were a total of 8,967 patients (69% male, average age 66 years) with HF (NYHA class I - 1%, class II - 54%, class III - 41%, class IV - 4 %) randomized to the placebo arm in the 27 studies. At trial completion (median duration 24 weeks, range 2 days to 106 weeks) the mean NP % change was - 6.5 +/- 31.2 %. Fourteen of 27 studies reported an NP decrease, and 13 reported an increase in NP values. Mean NP % change in trials of duration ≤ 24 weeks (n=15) was -12.4 +/- 29.1 %, whereas mean NP % change in trials > 24 weeks (n=12) was +4.5 +/- 32.5 % (p < 0.001 vs. ≤ 24 weeks).
Of the 27 RCTs, 4 trials included only patients with HF with preserved ejection fraction (HFpEF), 18 included only patients with HF with reduced ejection fraction (HFrEF), and 5 included both. The 4 trials with HFpEF patients had a total of 253 patients and had a mean NP % change of 9.0 +/- 28.4%. The 18 trials with HFrEF patients had a total of 7389 patients and had a mean NP % change of -1.3 +/- 27.0 % (p<0.001 vs. HFpEF)
Conclusion: In contemporary RCTs in patients with HF, NP responses in the placebo-group arm have wide variability, may increase or decrease, are different in patients with HFpEF or HFrEF, and are associated with the duration of the trial. The ability to quantify the contribution of placebo effects in the context of trial duration can help determine sample sizes and duration of study for trials involving biomarker endpoints.
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