Methods

Type of study: parallel randomised controlled trial

Setting and country: Ottawa Hospital, Canada

Number of centres: 1

Dates of trial (start and end): June 2012 to June 2015

Follow‐up period: 6 months

Power calculation: unclear

Participants

Number of participants: 9

Inclusion criteria:

• adults 18 years or older with documented MDS (including MDS subtype CMML) or AML (as defined by WHO criteria)

• severe thrombocytopenia defined as a platelet count of ≤ 10 x 10⁹/L documented on 2 consecutive samples at least 7 days apart

• receiving outpatient‐based supportive or palliative care including palliative cytoreductive, immunomodulatory, or hypomethylating therapy, e.g. hydroxyurea or low‐dose cytarabine, lenalidomide, azacytidine, or decitabine

• Eastern Cooperative Oncology Group (ECOG) performance status of 0 to 2

Exclusion criteria:

• high‐dose therapy in the past 2 months, e.g. AML‐type induction or consolidation therapy

• thrombocytopenia suspected to be due to immune or peripheral destruction

• splenomegaly, palpated at greater than 5 cm below the costal margin or greater than 20 cm on imaging

• alloimmune platelet refractoriness

• clinically relevant bleed (Grade 3 or higher) within the past 3 months

• coagulopathy (prothrombin time or activated partial thromboplastin more than 1.5 times the upper limit of normal or fibrinogen less than 2 g/L)

• require anticoagulant therapy, e.g. heparin, or antiplatelet therapy, e.g. aspirin

• significant renal impairment (creatinine more than 1.5 times the upper limit of normal)

• geographic inaccessibility resulting in the inability to comply with follow‐up visits

• pregnant or breastfeeding

• unwilling or unable to provide informed consent

Interventions

• Therapeutic platelet transfusion: platelet transfusions were given to treat documented clinically relevant bleeding defined as WHO bleeding of Grade 2 or greater.

• Prophylactic platelet transfusion: platelet transfusion (a single dose of random donor platelets (4 unit pool or random donor platelets or 1 apheresis unit) when the measured platelet count is < 10 x 10⁹/L.

Outcomes

Primary outcome measures:

Feasibility at 18 months:

• overall trial enrolment

• off‐protocol platelet transfusions

• total number of platelet transfusions per group

• participant compliance with daily self assessment of bleeding

Secondary outcome measures:

Bleeding events at 6 months' follow‐up:

• non‐cutaneous Grade 2 bleeding or higher by the WHO bleeding assessment scale

• Grade 3 bleeding or higher events: from randomisation to first bleeding event of Grade 3 of higher

• total number of red cell transfusions per group

• total number of hospital days per group

• number of completed daily bleeding assessments per group

• quality of life

• mortality

Assessment of outcomes

Bleeding assessment

Study participants were asked to complete a diary of a simple bleeding questionnaire. Participants received a short training session and written material training course on how to complete the bleeding assessment form. The bleeding assessment was performed at all study follow‐up visits and involved interview, physical exam, and review of daily bleeding forms. Participants were asked to report any non‐cutaneous Grade 2 or greater bleeding immediately to their treating physicians and the study team. All the self assessments of bleeding will be reviewed at each participant visit to ensure that all clinically relevant bleeding episodes have been captured.

Bleeding events and the assignment of the bleeding grade were performed by study personnel. The final bleeding grade was assigned independently by two blinded physicians.

Blood transfusions

All platelet and red cell transfusions were recorded, including the date of transfusion and the number of units given. The type of platelet components transfused (apheresis or buffy coat) was also documented. The indication for all transfusions, i.e. prophylactic or to treat bleeding, was documented.

Quality of life

This was one of the trial's secondary outcomes and was assessed using the EuroQol‐5 dimensions (EQ‐5D) questionnaire. Quality of life assessments were performed at baseline and at all subsequent participant visits.

The EQ‐5D, which is a health‐related quality of life instrument, comprises a health state classification followed by a health evaluation using a visual analogue scale (VAS). The VAS part provides a single global rating of self perceived health and is scored on a 0‐to‐100‐millimetre scale representing “the worst...” and “the best health you can imagine”, respectively (McCaffrey 2016).

Notes

Trial registration number: NCT01615146

Source(s) of funding and collaborator: Ottawa Hospital Research Institute, Canadian Blood Services, Canadian Institutes of Health Research (CIHR)

Conflicts of interest: unclear

Investigators: Alan Tinmouth, Ottawa Hospital Research Institute

Other

The trial was terminated due to poor recruitment.

Other study ID: OHREB 2011500

Risk of bias

Bias

Authors' judgement

Support for judgement

Random sequence generation (selection bias)

Low risk

Randomised controlled trial design using a web‐based randomisation method. "A local study nurse used a web‐based randomization system (permuted random blocks of two or four patients) to allocate consenting patients."

Allocation concealment (selection bias)

Low risk

Randomised controlled trial design using a web‐based randomisation method. "A local study nurse will use a web‐based randomization system (permuted random blocks of two or four patients) to allocate consenting patients"

Blinding of participants and personnel (performance bias)
All outcomes

High risk

Single‐blind study design

Blinding of outcome assessment (detection bias)
All outcomes

Low risk

Single‐blind trial; outcome assessors were blind to the intervention status. "Medical and research staff and investigators will be blinded to randomization scheme"

Incomplete outcome data (attrition bias)
All outcomes

Unclear risk

No information available to assess this domain

Selective reporting (reporting bias)

Unclear risk

No information available to assess this domain

Other bias

Unclear risk

No information available to assess this domain