The Use of Isocapnic Hyperventilation (iHV) for Treatment of Methanol Poisoned Patients

Methanol Poisoning Clinical Trial

— iHV-Met  

Official title:

The Use of Isocapnic Hyperventilation (iHV) for Treatment of Methanol Poisoned Patients

Clinical Trial Details — Status: Recruiting

Administrative data

• NCT number: NCT06173817
• Other study ID #: iHV-Met_2.0
• Secondary ID: U1111-1277-63604
• Status: Recruiting
• Phase: Phase 2/Phase 3
• Start date: December 20, 2023
• Est. completion date: June 30, 2026

Study information

• Verified date: December 2023
• Source: Oslo University Hospital
• Contact: Knut Erik Hovda, MD, Ph D
• Phone: +4799618356
• Email: knuterikhovda[@]gmail.com
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial 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.

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.

Recruitment information / eligibility

• Status: Recruiting
• Enrollment: 30
• Est. completion date: June 30, 2026
• Est. primary completion date: December 31, 2025
• Accepts healthy volunteers: No
• Gender: All
• Age group: 18 Years to 80 Years

Eligibility

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.

Related Conditions & MeSH terms

• Hyperventilation
• Methanol Poisoning
• Poisoning

Intervention

Device:
• isocapnic hyperventilation
isocapnic hyperventilation (iHV) increases the elimination of methanol to the extent that it could replace haemodialysis for elimination purposes when haemodialysis is not required for the correction of acidosis, and alcohol dehydrogenase (ADH) is completely blocked by an antidote.

Locations

Country	Name	City	State
Iran, Islamic Republic of	Loghman-Hakim Hospital,	Teheran

Sponsors (6)

Lead Sponsor	Collaborator
Oslo University Hospital	Baharloo Hospital, Teheran, Iran, Imam Reza Hospital, Mashhad University of Medical Sciences, Iran, Khorshid Hospital, Isfahan University of Medical Sciences, Iran, Loghman-Hakim Hospital, Teheran, Iran, Shohada-e-Tajrish Hospital, Teheran, Iran

Country where clinical trial is conducted

Iran, Islamic Republic of, 

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Characterization of methanol elimination kinetics, when iHV is utilized	T1/2 S-methanol (t1-t2) during iHV: Half-life of methanol in blood from start (t1) to end (t2) of treatment with iHV; T1/2 S-methanol (t0-t1) before iHV): Half-life of methanol in blood from t0 to t1 before start of treatment with iHV for evaluation of individual differences in kinetics	0-40 hours
Secondary	Characterization of methanol elimination kinetics, prior to iHV is utilized	T1/2 S-methanol (t0-t1) before iHV): Half-life of methanol in blood from t0 to t1 before start of treatment with iHV for evaluation of individual differences in kinetics	0-40 hours
Secondary	Serum formate kinetics	T1/2 S-formate before (t0-t1) before and after (t1-t2) (iHV): Half-life of formate in blood from t0 to t1 before start of treatment with iHV for evaluation of individual differences in kinetics	0-40 hours
Secondary	Elimination ratio of methanol	Evaluation of elimination ratio of methanol through breath vs. urine with or without iHV	0-40 hours
Secondary	Elimination ratio of formate	Evaluation of elimination ratio of formate through breath vs. urine with or without iHV	0-40 hours
Secondary	Feasibility of use of iHV in Iran	iHV is new in Iran. The process requires training to be implemented correctly. This will be evaluated by assessing protocol deviations related to iHV equipment and by interviewing study workers on their perceived competency using the iHV equipment.; This will not be reported in one value, but presented as text and used as an exploratory outcome to guide any future implementation of iHV in Iran	0-40 hours
Secondary	Tolerability by self reporting by patient	Patient tolerability of iHV as self reported by patient; This will be recorded using a five-level Likert Scale; 1 Did not tolerate iHV at all 2: Tolerated iHV sin shorter periods, but below therapeutic level 3: Barely tolerated iHV enough for therapeutic level 4 Tolerate iHV enough for therapeutic level 5: No discomfort and good toleration of iHV	0-40 hours
Secondary	Implementation of fomepizole in Iran	Perception of simplicity of use of fomepizole amongst doctors involved in the study This will be recorded using a five-level Likert Scale; 1 Fomepizole can not be used in the Iranian healthcare system 2: Fomepizole is difficult and require significant extra efforts to be used in the Iranian healthcare system 3: Fomepizole may be used the Iranian healthcare system with some extra effort 4 Fomepizole can easily be used the Iranian healthcare system with little extra effort 5: Fomepizole can easily be used the Iranian healthcare system with no extra effort	through study completion, estimated 2 years
Secondary	Evaluation of fomepizole elimination during iHV	S-fomepizole analyzes from t1-t2. Pending availability of fomepizole analyzes	0-4 hours
Secondary	Length of ICU- and hospital stay	Length during treatment with iHV	from stdy start to death or discharge ICU, expected average 30 hours
Secondary	Need for haemodialysis	Document type and degree of haemodialysis. Indication for such treatment is by the discretion of the local investigator. If S methanol >5mM after 26hrs (T1/2 50-80hrs during fomepizole treatment without haemodialysis (8)) or if patient becomes increasingly acidotic in spite of adequate antidote treatment.	0- 40 hours
Secondary	Adverse events	Adverse events, including death, will be defined according to Good Clinical Practice guidelines by the International Conference on Harmonization of technical requirements for registration of pharmaceuticals for human use. All adverse events will be registered in this trial and reported in accordance with local regulations in Iran.; Adverse events also include medical device deficiency of the isocapnic hyperventilation system	through study completion, estimated 2 years