|- candidate number||27170|
|- NTR Number||NTR6427|
|- ISRCTN||ISRCTN no longer applicable|
|- Date ISRCTN created|
|- date ISRCTN requested|
|- Date Registered NTR||4-mei-2017|
|- Secondary IDs||P16.025 NL55794.058.15|
|- Public Title||The BREATH study|
|- Scientific Title||Effect of neuromuscular blockade and reversal by sugammadex versus neostigmine on breathing when hypoxic or hypercapnic in volunteers|
|- hypothesis||A. Rocuronium will induce impairment of carotid body function through blockade of cholinergic neurotransmission in carotid bodies resulting in a reduced or absent ventilatory response to isocapnic hypoxia. |
B. Sugammadex will completely restore carotid body function following rocuronium administration with full reversal of the ventilatory response to isocpanic hypoxia within 2 min.
C. Neostigmine will cause a protracted reversal of the carotid body function following rocuronium administration with full reversal within 40-60 min.
|- Healt Condition(s) or Problem(s) studied||Neuromuscular blockade, Carotid bodies|
|- Inclusion criteria||Healthy male volunteers aged 18 and older with a body mass index < 30 kg/m2.|
|- Exclusion criteria||Known or suspected neuromuscular disorders impairing neuromuscular function; allergies to muscle relaxants, anesthetics or narcotics; a (family) history of malignant hyperthermia or any other muscle disease; any medical, neurological or psychiatric illness (including a history of anxiety).|
|- mec approval received||yes|
|- multicenter trial||no|
|- Type||2 or more arms, randomized|
|- planned startdate ||6-jun-2017|
|- planned closingdate||6-mrt-2018|
|- Target number of participants||36|
|- Interventions||- Partial neuromuscular block with rocuronium|
- Hypoxic and hypercapnic ventilatoy respons
- Antagonizing neuromuscular block with either neostigmine or sugammadex or placebo
|- Primary outcome||- The effect of partial neuromuscular blockade (NMB; TOF ratio 0.8 and 0.6) induced by low-dose rocuronium on the ventilatory response to isocapnic hypoxia and the effect over time (from TOF 0.6 to TOF 1.0) of the reversal by sugammadex, neostigmine or placebo in healthy volunteers|
|- Secondary outcome||To assess the effect of partial NMB (TOF ratio 0.6) induced by low-dose rocuronium on the ventilatory response to hypercapnia and effect over time (from TOF 0.6 to TOF 1.0) of the reversal by sugammadex, neostigmine or placebo in healthy volunteers.|
|- Timepoints||Baseline ventilation, ventilatory measurements every 5 min. |
|- Trial web site|
|- status||open: patient inclusion|
|- CONTACT FOR PUBLIC QUERIES||Prof. Dr. Albert Dahan|
|- CONTACT for SCIENTIFIC QUERIES||Prof. Dr. Albert Dahan|
|- Sponsor/Initiator ||Leiden University Medical Center (LUMC)|
(Source(s) of Monetary or Material Support)
|Leiden University Medical Center (LUMC)|
|- Brief summary||This is a randomized, double blind, 3-arm, placebo controlled parallel study on the influence of reversal of a partial NMB on carotid body function following rocuronium administration. Healthy volunteers will be randomized to receive either placebo (Group1, n = 12), neostigmine (1 mg. n =12) or sugammadex (2 mg/kg, n = 12) following a continuous rocuronium infusion for 120 min aimed at a TOF ratio of 0.8 for 1 h followed by 0.6 for another hour. Prior to the rocuronium infusion and during the infusion, ventilatory responses to isocapnic 2-min hypoxic pulses will be obtained as well as the (hyperoxic) ventilatory response to hypercapnia. After the 120 min infusion and the administration of reversal agents, the ventilatory response to hypoxic pulses will be obtained at 5 min interval for at least 60 min. In case the response has not returned to pretreatment control values, additional responses will be obtained. Hereafter, a final ventilatory response to carbon dioxide will be obtained (at hyperoxic conditions).|
|- Main changes (audit trail)||Amendement 30-jul-2018: |
The study was amended as follows:
- After baseline respiratory measurements were obtained (acute hypoxic response, AHR, and the hypercapnia ventilatory response, HCVR), rocuronium was administered and titrated to a TOF ratio of 0.7, rather than to 0.6 and 0.8. After the target of 0.7 was reached the respiratory measurements were repeated.
- Thereafter the reversal agents (sugammadex, neostigmine, or placebo) were administered according to randomization.
- Since reversal was relatively fast, we performed two hypoxic steps AHR and one HCVR one specified time point.
|- RECORD||4-mei-2017 - 6-aug-2018|