Conversion From Parenteral to Oral Methadone. (RATIOMTD)

This study is currently recruiting participants. (see Contacts and Locations)
Verified April 2013 by L'Hospitalet de Llobregat
Sponsor:
Collaborators:
Hospital Arnau de Vilanova, Lleida (Spain)
Hospital Universitario La Paz, Madrid (Spain)
Information provided by (Responsible Party):
JESÚS GONZÁLEZ BARBOTEO, L'Hospitalet de Llobregat
ClinicalTrials.gov Identifier:
NCT01836328
First received: April 17, 2013
Last updated: April 5, 2014
Last verified: April 2013
  Purpose

The majority of current studies regarding the use of methadone (MTD) in the treatment of cancer pain are focused in its administration via the oral route (PO). The ratio considered from VO to parenteral route (BP) is 2:1. Academic literature assumes the ratio from BP to VO to be 1:2. In our unit, we use MTD in the context of ROP and not as the last opioid. If face with a situation where there is a good control of pain with MTD BP, usually we move to VO. We have observed that the traditional ratio tend to produce certain toxicity problems. Because of this, we have proposed a new ratio of conversion from PAR MTD to oral MTD, i.e. 1:1.2


Condition Intervention Phase
Pain
Drug: Parenteral /oral methadone ratio 1:2
Drug: Parenteral /oral methadone ratio 1:1.2
Phase 3

Study Type: Interventional
Study Design: Allocation: Randomized
Endpoint Classification: Safety/Efficacy Study
Intervention Model: Parallel Assignment
Masking: Double Blind (Subject, Outcomes Assessor)
Primary Purpose: Supportive Care
Official Title: Prospective Randomized Simple Blinded Study Comparing Two Conversion Ratios From Parenteral to Oral Methadone in Patients With Cancer Pain.

Resource links provided by NLM:


Further study details as provided by L'Hospitalet de Llobregat:

Primary Outcome Measures:
  • Proportion of intoxicated patients in each groups [ Time Frame: at 3 days after opioid rotation to Oral Methadone ] [ Designated as safety issue: Yes ]

Secondary Outcome Measures:
  • Parenteral/oral MTD final ratio in patients considered as "failure" [ Time Frame: One week after the change from pareteral to oral MTD ] [ Designated as safety issue: No ]

Estimated Enrollment: 44
Study Start Date: August 2011
Estimated Study Completion Date: March 2015
Estimated Primary Completion Date: December 2014 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Active Comparator: Parenteral /oral methadone ratio 1:2

Far advanced cancer patients with cancer pain hospitalized, and treated with PMTD undergo a preliminary 48 hours observation phase.

Blinded evaluators assess pain management and treatment toxicity and determine an OPTIMISED DOSE of parenteral METHADONE (pain control without toxicity) for each patient.

Only patients with a correct control of pain and without significant toxicity throughout this period are eligible for randomization.

INTERVENTION: Patients randomized to this arm will receive the double of OPTIMISED DOSE of parenteral METHADONE, orally every 24h in 3 administrations during the following 3 days.

Drug: Parenteral /oral methadone ratio 1:2
Other Name: Eptadone (1mg/ml) oral solution
Experimental: Ratio 1:1.2

Far advanced cancer patients with cancer pain hospitalized, and treated with PMTD undergo a preliminary 48 hours observation phase.

Blinded evaluators assess pain management and treatment toxicity and determine an OPTIMISED DOSE of parenteral METHADONE (pain control without toxicity) for each patient.

Only patients with a correct control of pain and without significant toxicity throughout this period are eligible for randomization.

INTERVENTION: Patients randomized to this arm will receive the following Oral Methadone dose: 20% increase of optimised parenteral methadone dose every 24h in 3 administrations during the following 3 days.

Drug: Parenteral /oral methadone ratio 1:1.2
Other Name: Eptadone (1mg/ml) oral solution

Detailed Description:

OBJECTIVE: To compare the different ratios of conversion from MTD VP to MTD PO. To verify the presence of lower toxicity in the ratio 1:1.2 against 1:2 while still maintaining a good control of pain in patients with advanced cancer that are hospitalized in different palliative care units.

METHODOLOGY: Prospective randomized single blind study in patients with cancer pain treated with parenteral MTD and that would move into MTD oral provided there is good control of pain. The patients will be randomly split into two groups: (Group A = ratio 1:1.2 and Group B=ratio 1:2). Patients will be evaluated during the three days before the switch is applied, the day of the change and during the 3 days post-ROP. The patients who display significant toxicity and/or bad analgesic control within the first 72 hours post-ROP will be considered negative cases. The size of the sample required will include 46 patients distributed in balanced groups in order to obtain a size effect of 30% and a statistical power of 80%. The significance level will be 0.05 for two tails.

STATISTIC ANALYSIS: By means of Chi-squared to compare the proportion of Opioid Rotation (OR) failure in both groups of study.

  Eligibility

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
Accepts Healthy Volunteers:   No
Criteria

Inclusion Criteria:

  • diagnosis of advanced disease of any type of malignancy;
  • >18 years old at the time of inclusion;
  • for inclusion in the screening phase, the patient is a candidate to pass parenteral methadone to oral methadone (MTD) following to the physician criteria.
  • for inclusion in the assessment phase should follow: presence of cancer pain controlled with no significant toxicity with MTD VP for 48h. Be considered controlled pain and absence of significant toxicity due to MTD, as the definitions given in the general protocol;

    e) signing the informed consent form.

Exclusion Criteria:

  1. impairment cognitive status that interferes with the assessment;
  2. diagnosis of psychiatric disorders at the time of recruitment that alters the ability to evaluate;
  3. presence of side effects due to chemotherapy and / or radiotherapy prior to the change of route of administration, taking into account the following two criteria:

    • For patients on a protocol of successive cycles of chemotherapy (no change in chemotherapy regimen), having presented side effects due to chemotherapy in the 15 days prior to the change of route of administration as clinically and following the recommendations of the 2011 4th ed Oncomecum of the Spanish Society of Medical Oncology and deemed that may interfere with the assessment of the primary endpoint.
    • For patients starting a new protocol of chemotherapy or radiotherapy, have submitted side effects due to such treatment in the 28 days prior to the change of route of administration based on clinical judgment and following the recommendations of the Oncomecum 2011 4th ed. of the Spanish Society of Medical Oncology and deemed that may interfere with the assessment of the primary endpoint.
  4. invasive anesthesic techniques have been made during the 3 days before changing to oral parenteral;
  5. patients at agony.
  Contacts and Locations
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: NCT01836328

Contacts
Contact: JESÚS GONZÁLEZ-BARBOTEO, MD 0034932607789 jgonzalez@iconcologia.net

Locations
Spain
Institut Català D'Ncologia. Hospital Duran Y Reynals Recruiting
L'hospitalet de Llobregat, Barcelona, Spain, 08907
Contact: JESÚS GONZÁLEZ-BARBOTEO, MD    0034932607789    jgonzalez@iconcologia.net   
Principal Investigator: JESÚS GONZÁLEZ-BARBOTEO, MD         
Sub-Investigator: JOSEP PORTA-SALES, PHD         
Sub-Investigator: CRISTINA GARZÓN-RODRÍGUEZ, PHD         
Hospital Arnau de Vilanova Recruiting
Lleida, Spain, 25198
Contact: MARÍA NABAL-VICUÑA, PHD    0034973240100 ext 5243    mnabal@secpal.com   
Principal Investigator: MARÍA NABAL-VICUÑA, PHD         
Sub-Investigator: JAUME CANAL-SOTELO, MD         
Hospital Universitario La Paz Recruiting
Madrid, Spain, 28046
Contact: Leyre Díez Porres, PhD    003491 727 70 57    ldiezporres@gmail.com   
Principal Investigator: Leyre Diez Porres, PhD         
Sub-Investigator: Alberto Alonso Babarro, MD         
Sub-Investigator: Yolanda Vilches, MD         
Sponsors and Collaborators
L'Hospitalet de Llobregat
Hospital Arnau de Vilanova, Lleida (Spain)
Hospital Universitario La Paz, Madrid (Spain)
Investigators
Principal Investigator: JESÚS GONZÁLEZ-BARBOTEO, MD INSTITUT CATALÀ D'ONCOLOGIA. HOSPITAL DURAN I REYNALS
  More Information

Publications:
Responsible Party: JESÚS GONZÁLEZ BARBOTEO, MEDICAL DOCTOR, L'Hospitalet de Llobregat
ClinicalTrials.gov Identifier: NCT01836328     History of Changes
Other Study ID Numbers: RATIOMTD-010810, 2010-024092-39, EC10-133
Study First Received: April 17, 2013
Last Updated: April 5, 2014
Health Authority: Spain: Agencia Española de Medicamentos y Productos Sanitarios

Keywords provided by L'Hospitalet de Llobregat:
Methadone
Pain
Neoplasms
Ratio

Additional relevant MeSH terms:
Methadone
Analgesics, Opioid
Analgesics
Sensory System Agents
Peripheral Nervous System Agents
Physiological Effects of Drugs
Pharmacologic Actions
Central Nervous System Agents
Therapeutic Uses
Central Nervous System Depressants
Antitussive Agents
Respiratory System Agents
Narcotics

ClinicalTrials.gov processed this record on July 23, 2014