Week 8 Reading: MISTRAL Trial (Wode et al., 2020)

Question 1

What was the background of the MISTRAL trial?

Answer 1

• most pancreatic cancer patients present with advanced stage at diagnosis with extremely short expected
  survival and few treatment options
• we need symptom relief through methods
• especially to participants who are ineligible to chemotherapy
• mistletoe extract is a potential solution

Question 2

What was the objective of the MISTRAL trial?

Answer 2

To assess the value of mistletoe extract as a complement to standard treatment (palliative chemotherapy or best supportive care) in advanced pancreatic cancer patients with regard to overall survival and healthrelated quality of life

Question 3

What was the study design of MISTRAL?

Answer 3

Prospective, randomised, double-blind, multicentre, parallel group and placebo-controlled

Phase III Clinical trial

Question 4

What were the methods of MISTRAL?

Answer 4

290 participants are randomly assigned to placebo or mistletoe extract given subcutaneously in increasing dosage
from 0.01 to 20 mg three times per week for 9 months. Stratification is performed for site and palliative chemotherapy.

Two ancillary studies on sub-sets of participants are nested in the trial: (an ancillary study is an independent research project that uses samples or data from a parent study)

1. A biomarker study collecting blood samples
2. A cross-sectional qualitative study with semistructured face-to-face interviews

Question 5

What are the key elements that the authors felt readers should know about the design methods they planned to employ?

Answer 5

• The study design and how each element of the design would be carried out
  
  • Phase III Clinical Trial: Prospective, randomised, double-blind, multicentre, parallel group and placebo-controlled
  • How interventions are assigned, randomised, concealed, implemented, blinded
• Exact intervention with trial doses and procedure
• Conditions for terminating trial intervention and timeframe of study
• Relevant concomitant care permitted during intervention
• Strategies to improve adherence to interventions, promote follow up
• Post-trial care
• Adverse event reporting and harms

Question 6

What are the key elements that the authors felt readers should know about the data collection methods they planned to employ?

Answer 6

Primary outcome - overall survival

Secondary outcomes - generic and disease-specific aspects of HRQoL using validated questionnaires, body weight, corticosteroid use, adverse events, ECOG performance, drug accounts/changes and interruptions

• Statistical methods for analysing outcomes (ie in relation to hypotheses)
• Secure data management
• Confidentiality
• Analysis datasets and different analyses models conducted (ie. full analysis set and then per protocol, then safety analysis)

Question 7

Who was involved in the MISTRAL research team?

Answer 7

Trial steering
Data manager
Coordinating investigator
Principle investigators (ancillary studies)
Principle investigators and study nurses at study sites

Data monitoring committee

Question 8

What were the sampling and recruitment methods of MISTRAL?

Answer 8

• Academic multicentre study
• Nine participating hospitals, a few hospitals participating in ancillary studies

potential participants are identified at
multidisciplinary conferences and/or at therapy conferences at associated surgical departments, at the
oncology departments of the stud centres or in
associated palliative home care units.

ancillary studies
1. For the biomarker study, participants are recruited
consecutively at baseline visit.
2. For the qualitative study, participants are recruited
in-between visit three and four by phone-call