Midazolam and morphine to alleviate symptoms at the end of life in patients on acute geriatric wards

2024-517763-22-00 Therapeutic use (Phase IV) Ended

Start 3 Feb 2025 · End 31 Dec 2025 · Status Ended · 1 EU/EEA countries · 2 sites

Overview

Sponsor-declared trial summary

Phase Therapeutic use (Phase IV)
Status Ended
Participants planned 300
Countries 1
Sites 2

Symptom treatment in the last days of life of geriatric patients

1. To characterize the relationship between morphine dosing and the time to symptom control (discomfort/pain and dyspnea) in geriatric patients during their last days of life. 2. To characterize the relationship between midazolam dosing and the time to symptom control (discomfort/pain, dyspnea and agitation) in geriatr…

Key facts

Sponsor
UZ Leuven
Participant type
Patients
Age range
65+ years
Gender
Male and Female
Therapeutic area
Diseases [C] - Pathological Conditions, Signs and Symptoms [C23]
Trial duration
3 Feb 2025 → 31 Dec 2025
Decision date (initial)
2025-01-20
Transition trial
No
Low-intervention
Yes
Rare-disease indication
No
Vulnerable population
Yes

Trial design

CTIS Part I — objectives, methods, condition coding

Main objective

Scope: Pharmacodynamic, Pharmacokinetic, Safety, Dose response

1. To characterize the relationship between morphine dosing and the time to symptom control (discomfort/pain and dyspnea) in geriatric patients during their last days of life.
2. To characterize the relationship between midazolam dosing and the time to symptom control (discomfort/pain, dyspnea and agitation) in geriatric patients during their last days of life.
3. To characterize the relationship between morphine dosage and the occurrence of adverse drug reactions in geriatric patients during their last days of life.
4. To characterize the relationship between midazolam dosage and the occurrence of adverse drug reactions in geriatric patients during their last days of life.

Secondary objectives 6

  1. 5. What factors influence morphine pharmacokinetics in geriatric patients during their last days of life?
  2. 6. What factors influence morphine pharmacodynamics in geriatric patients during their last days of life?
  3. 7. What factors influence midazolam pharmacokinetics in geriatric patients during their last days of life?
  4. 8. What factors influence midazolam pharmacodynamics in geriatric patients during their last days of life?
  5. 9. To characterize the relationship between morphine and midazolam dosages and the time until death after establishment of the dying phase?
  6. 10. How do creatinine, urea, albumin, bilirubin, GGT, ALT, sodium, CRP and urinary creatinine evolve in geriatric patients during their last days of life?

Conditions and MedDRA coding

Symptom treatment in the last days of life of geriatric patients

Eligibility criteria

Principal inclusion / exclusion criteria as submitted by sponsor

Inclusion criteria 2

  1. Hospitalization on the acute geriatric ward
  2. Patient expected to die in the following hours or days

Exclusion criteria 1

  1. Expected discharge from the hospital before death

Endpoints

Primary and secondary outcome measures (English text)

Primary endpoints 3

  1. Morphine and midazolam doses, time of administration and route of administration
  2. Symptom control: discomfort scale, agitation/sedation scale and dyspnea scale
  3. Adverse reactions: : nausea, vomiting, hallucinations, constipation, myoclonus, pruritus, hiccups, respiratory rate and other adverse reactions occurring that are related to the Morphine and Midazolam injection according to the nurse or doctor.

Secondary endpoints 3

  1. Morphine, morphine-3-glucuronide and morphine-6-glucuronide plasma concentrations
  2. Midazolam and alpha-hydroxy-midazolam glucuronide plasma concentrations
  3. Blood creatinine, urea, albumin, bilirubin, GGT, ALT, sodium, CRP and urinary creatinine concentrations

Investigational products

Investigational medicinal products (IMPs), comparators, placebo, auxiliary

Test 2

Dobutamine Hydrochloride

SCP112629113 · ATC

Active substance
Dobutamine Hydrochloride
Route of administration
INTRAVENOUS/SUBCUTANEOUS/INTRAMUSCULAR
Max daily dose
300 mg milligram(s)
Max total dose
4200 mg milligram(s)
Max treatment duration
14 Day(s)
Authorisation status
Authorised
ATC code
N05CD08 — MIDAZOLAM
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Morphine

SCP1000773 · ATC

Active substance
Morphine
Route of administration
INTRAVENOUS/SUBCUTANEOUS/INTRAMUSCULAR
Max daily dose
300 mg milligram(s)
Max total dose
4200 mg milligram(s)
Max treatment duration
14 Day(s)
Authorisation status
Authorised
ATC code
N02AA01 — MORPHINE
Marketing authorisation
-
Paediatric formulation
No
Orphan designation
No
Modified vs. Marketing Authorisation
No

Sponsors and contacts

Sponsor organisations, regulatory contacts, third parties

UZ Leuven

Sponsor organisation
UZ Leuven
Address
Herestraat 49
City
Leuven
Postcode
3000
Country
Belgium

Scientific contact point

Organisation
UZ Leuven
Contact name
Tim Biesbrouck

Public contact point

Organisation
UZ Leuven
Contact name
Tim Biesbrouck

Locations

1 EU/EEA country · 2 investigational sites

By country

CountryMS statusPlanned subjectsSites
Belgium Ended 300 2
Rest of world 0

Investigational sites

Belgium

2 sites · Ended
UZ Leuven
Geriatric Medicine, Herestraat 49, 3000, Leuven
Universitair Ziekenhuis Gent
Geriatric Medicine, Corneel Heymanslaan 10, 9000, Gent

Country notifications

Trial-start, recruitment-start, end and early-termination notifications submitted per Member State

Country Trial startTrial end Recruitment startRecruitment end Early termination
Belgium 2025-02-03 2025-12-31 2025-02-03

Results and documents

Annex IV summary of results, Annex V layperson summary, and all documents registered in CTIS for this trial

Documents 16 files

Public protocol annexes, IB summaries, regulatory submissions and post-authorisation documents registered in CTIS.

TypeTitleVersion
Protocol (for publication) D1_Protocol 2024-517763-22 4
Recruitment arrangements (for publication) K1_Recruitment arrangements 2
Subject information and informed consent form (for publication) Informed consent procedure 2
Subject information and informed consent form (for publication) L1_SIS and ICF patient observational 2
Subject information and informed consent form (for publication) L1_SIS and ICF patient PK sub-study dutch 3
Subject information and informed consent form (for publication) L1_SIS and ICF relative observational 2
Subject information and informed consent form (for publication) L1_SIS and ICF relative PK sub-study dutch 3
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Midazolam 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Midazolam 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Morphine 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Morphine 1
Summary of Product Characteristics (SmPC) (for publication) G2_SmPC Morphine 1
Synopsis of the protocol (for publication) D1_Protocol synopsis_DU 2024-517763-22 2
Synopsis of the protocol (for publication) D1_Protocol synopsis_ENG 2024-517763-22 2
Synopsis of the protocol (for publication) D1_Protocol synopsis_FR 2024-517763-22 2
Synopsis of the protocol (for publication) D1_Protocol synopsis_NL 2024-517763-22 2

Application history

2 submissions — initial application plus substantial / non-substantial modifications

#TypeCodeSubmittedReference MSConclusionDecision date
1 INITIAL IN 2024-09-24 Belgium Acceptable with conditions
2025-01-15
2025-01-20
2 SUBSTANTIAL MODIFICATION SM-1 2025-11-13 Belgium Acceptable
2026-01-29
2026-01-29