Clinical trial NCT06173817: The Use of Isocapnic Hyperventilation (iHV) for Treatment of Methanol Poisoned Patients
Official title: The Use of Isocapnic Hyperventilation (iHV) for Treatment of Methanol Poisoned Patients
Study type: INTERVENTIONAL
Overall status: RECRUITING
Phase: PHASE2
PHASE3
Conditions: Methanol Poisoning
Keywords: isocapnic hyperventilation
Lead sponsor: Oslo University Hospital
Sponsor class: OTHER
Collaborators: name: Loghman-Hakim Hospital, Teheran, Iran
name: Shohada-e-Tajrish Hospital, Teheran, Iran
name: Baharloo Hospital, Teheran, Iran
name: Imam Reza Hospital, Mashhad University of Medical Sciences, Iran
name: Khorshid Hospital, Isfahan University of Medical Sciences, Iran
First posted: 2023-12-18
Enrollment: 30
Sex: ALL
Minimum age (years): 18
Maximum age (years): 80
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: no
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Prospective, single arm study

* Enrolment target: 30 evaluable patients
* Intervention: standard of care with sodium bicarbonate and fomepizole, plus iHV device treatment
* Rescue therapy: haemodialysis at investigators discretion
Primary purpose: TREATMENT

Brief summary: The projects investigate if treatment with isocapnic hyperventilation can eliminate methanol from the body in a similar manner to dialysis. This is achieved by administering the antidote (fomepizole) and let the patient breathe on a isocapnic hyperventilation device while samples of blood, urine and maybe the breath are collected to measure the contents of methanol and its metabolites.

Detailed description: Isocapnic hyperventilation (iHV) The normal physiology breathing is a careful balance between the number of breaths per minute (rate/min) and the depth of each breath (tidal volume, Vt). Together they make up the minute ventilation (MV), where MV= rate x Vt). To maintain stable homeostasis in the organism, the minute ventilation is closely regulated to maintain adequate uptake of oxygen and adequate elimination of the carbon dioxide (CO2) that is produced by the metabolism. Too low minute ventilation leads to a buildup of CO2 and decrease in blood pH (respiratory acidosis), while hyperventilation (too high minute ventilation) leads to an excess loss of CO2 and increase in blood pH (respiratory alkalosis). The same mechanism will also enable the organism to compensate any metabolic disturbances (up to a certain point): A metabolic acidosis will be counteracted by a hyperventilation, whereas a metabolic alkalosis will be counteracted by a hypoventilation, both with the ultimate goal of keeping the acidity (as given by the pH) as closely regulated as possible.

The concept of isocapnic hyperventilation (iHV) allows the person to hyperventilate while keeping the CO2 within normal limits at the same time. The ClearMate (Thornhill Research Inc., Canada) adds CO2 to the inspired air to compensate to the increased loss induced by the increased minute ventilation. This means that hyperventilation can occur, and a wash-out of volatile substances such as methanol will happen without disrupting the important CO2 balance.

Eligibility criteria: Inclusion Criteria:

* Adult patients, men \& women diagnosed with methanol poisoning
* Serum-methanol ≥ 50 mg/dL (16 mM)
* pH ≥ 7.0, and correctable by bicarbonate infusion
* no (newly developed) visual disturbances

Exclusion Criteria:

* Acidosis requiring haemodialysis (pH \<7.0), or acidosis that is not responding in spite of aggressive buffer (bicarbonate) treatment within maximum 1-2 hours.
* Comatose patients
* Newly developed visual disturbances
* ADH not fully blocked with antidotes, and not responding to additional dosing of fomepizole. Will be identified by a continuous or increasing anion gap (AG) or Base Excess (BE) on the blood gas machine.

Primary outcomes:
measure: Characterization of methanol elimination kinetics, when iHV is utilized
timeFrame: 0-40 hours
Secondary outcomes:
measure: Characterization of methanol elimination kinetics, prior to iHV is utilized
timeFrame: 0-40 hours
measure: Serum formate kinetics
timeFrame: 0-40 hours
measure: Elimination ratio of methanol
timeFrame: 0-40 hours
measure: Elimination ratio of formate
timeFrame: 0-40 hours
measure: Feasibility of use of iHV in Iran
timeFrame: 0-40 hours
measure: Tolerability by self reporting by patient
timeFrame: 0-40 hours
measure: Implementation of fomepizole in Iran
timeFrame: through study completion, estimated 2 years
measure: Evaluation of fomepizole elimination during iHV
timeFrame: 0-4 hours
measure: Length of ICU- and hospital stay
timeFrame: from stdy start to death or discharge ICU, expected average 30 hours
measure: Need for haemodialysis
timeFrame: 0- 40 hours
measure: Adverse events
timeFrame: through study completion, estimated 2 years
Other outcomes:
Locations:
city: Teheran
country: Iran, Islamic Republic of
facility: Loghman-Hakim Hospital,
Study officials:
affiliation: The Norwegian CBRNE Centre, Department of Acute Medicine, Oslo University Hospital Oslo, Norway
name: Knut Erik Hovda, MD, Ph D
role: PRINCIPAL_INVESTIGATOR
References: