Trial Outcomes & Findings for A Study of JNJ-30979754 (Decitabine) in Patients With Myelodysplastic Syndrome (NCT NCT00796003)

Last Updated: 2013-12-09

Results Overview

IWG response criteria (2000) - CR: bone marrow evaluations show \< 5% blasts; no dysplasia; normal maturation of all cell lines and peripheral blood shows hemoglobin ≥ 11 g/dL; neutrophils ≥ 1,500/mL; platelets ≥ 100,000/mL; 0% blasts; no dysplasia and PR: same as CR, except blasts decrease by ≥ 50% or lower French-American-British (FAB) classification of Myelodysplastic Syndromes.

Recruitment status

COMPLETED

Study phase

PHASE1

Target enrollment

39 participants

Primary outcome timeframe

Up to 1 years after the last participant enrolled

Results posted on

2013-12-09

Participant Flow

39 participants were enrolled at multiple sites in Japan.

9 participants were enrolled and treated in Phase 1. 36 participants (including 6 participants from Phase I) were enrolled in Phase II. 34 participants were treated and 2 participants were untreated in Phase II.

Participant milestones

Participant milestones
Measure	Phase I: 15 mg/m2 15 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of a 4-Week (28-day) Cycle 1	Phase I and II: 20 mg/m2 Phase I: 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of a 4-Week (28-day) Cycle 1. Phase II: 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) other cycles (except Cycle I)
Overall Study STARTED	3	36
Overall Study Treated	3	34
Overall Study COMPLETED	0	7
Overall Study NOT COMPLETED	3	29

Reasons for withdrawal

Reasons for withdrawal
Measure	Phase I: 15 mg/m2 15 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of a 4-Week (28-day) Cycle 1	Phase I and II: 20 mg/m2 Phase I: 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of a 4-Week (28-day) Cycle 1. Phase II: 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) other cycles (except Cycle I)
Overall Study Disease Progression	2	13
Overall Study Adverse Event	1	7
Overall Study Specified organ function not met	0	1
Overall Study Physician Decision	0	4
Overall Study Withdrawal by Subject	0	1
Overall Study Other	0	1
Overall Study Participants Not treated	0	2

Baseline Characteristics

A Study of JNJ-30979754 (Decitabine) in Patients With Myelodysplastic Syndrome

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Phase I: 15 mg/m2 n=3 Participants 15 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of a 4-Week (28-day) Cycle 1	Phase I and II: 20 mg/m2 n=34 Participants Phase I: 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of a 4-Week (28-day) Cycle 1. Phase II: 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) other cycles (except Cycle I)	Total n=37 Participants Total of all reporting groups
Age Continuous	68.7 Years STANDARD_DEVIATION 2.08 • n=5 Participants	68.5 Years STANDARD_DEVIATION 7.09 • n=7 Participants	68.5 Years STANDARD_DEVIATION 6.81 • n=5 Participants
Age, Customized <65 years	0 Participants n=5 Participants	10 Participants n=7 Participants	10 Participants n=5 Participants
Age, Customized >= 65 and <= 74 years	3 Participants n=5 Participants	17 Participants n=7 Participants	20 Participants n=5 Participants
Age, Customized >=75 years	0 Participants n=5 Participants	7 Participants n=7 Participants	7 Participants n=5 Participants
Sex: Female, Male Female	0 Participants n=5 Participants	8 Participants n=7 Participants	8 Participants n=5 Participants
Sex: Female, Male Male	3 Participants n=5 Participants	26 Participants n=7 Participants	29 Participants n=5 Participants

PRIMARY outcome

Timeframe: Up to 1 years after the last participant enrolled

Population: Full Analysis Set (FAS): 34 participants were included in this analysis set for Phase II

Outcome measures

Outcome measures
Measure	Phase II: 20 mg/m2 n=34 Participants 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles	Phase I: 20 mg/m2 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of a 4-Week (28-day) Cycle 1	Phase II: 20 mg/m2 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles
Phase II: Overall Remission Rate (ORR): Number of Participants Who Achieved Complete Remission (CR)+Partial Remission (PR) - as Per International Working Group (IWG) Response Criteria (2000) CR	7 Participants	—	—
Phase II: Overall Remission Rate (ORR): Number of Participants Who Achieved Complete Remission (CR)+Partial Remission (PR) - as Per International Working Group (IWG) Response Criteria (2000) PR	2 Participants	—	—

PRIMARY outcome

Timeframe: Up to 1.5 years after the last participant enrolled

Population: Safety Population: 9 participants in Phase I and 34 participants in Phase II were evaluated for safety

Outcome measures

Outcome measures
Measure	Phase II: 20 mg/m2 n=3 Participants 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles	Phase I: 20 mg/m2 n=6 Participants 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of a 4-Week (28-day) Cycle 1	Phase II: 20 mg/m2 n=34 Participants 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles
Phase I and II: Number of Participants Who Experienced Adverse Events	3 Participants	6 Participants	34 Participants

SECONDARY outcome

Timeframe: Before dosing (Pre-dose), 30 min, 60 min (end of infusion), 65 min, 75 min, 90 min, 120 min, 180 min, 240 min after the start of decitabine infusion on Day 1 and Day 5 of 28-Days Cycle 1

Population: Pharmacokinetic Population: 8 participants were evaluated for pharmacokinetic analysis

Outcome measures

Outcome measures
Measure	Phase II: 20 mg/m2 n=3 Participants 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles	Phase I: 20 mg/m2 n=5 Participants 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of a 4-Week (28-day) Cycle 1	Phase II: 20 mg/m2 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles
Phase I: Maximum Observed Plasma Concentration of Decitabine (Cmax) Day 1	151.7 ng/mL Standard Deviation 28.729	166.4 ng/mL Standard Deviation 17.170	—
Phase I: Maximum Observed Plasma Concentration of Decitabine (Cmax) Day 5	142.0 ng/mL Standard Deviation 40.635	190.6 ng/mL Standard Deviation 54.679	—

SECONDARY outcome

Timeframe: Before dosing (Pre-dose), 30 min, 60 min (end of infusion), 65 min, 75 min, 90 min, 120 min, 180 min, 240 min after the start of decitabine infusion on Day 1 and Day 5 of 28-Days Cycle 1

Population: Pharmacokinetic Population: 8 participants were evaluated for pharmacokinetic analysis

Area under the curve from time zero to extrapolated infinite time (AUC Infinity) and area under the curve from time zero to last quantifiable concentration (AUC Last).

Outcome measures

Outcome measures
Measure	Phase II: 20 mg/m2 n=3 Participants 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles	Phase I: 20 mg/m2 n=5 Participants 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of a 4-Week (28-day) Cycle 1	Phase II: 20 mg/m2 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles
Phase I: Area Under the Plasma Concentration-time Curve (AUC) AUC Last - Day 1	149.0 ng*h/mL Standard Deviation 41.102	155.2 ng*h/mL Standard Deviation 15.754	—
Phase I: Area Under the Plasma Concentration-time Curve (AUC) AUC Last - Day 5	136.0 ng*h/mL Standard Deviation 37.855	152.0 ng*h/mL Standard Deviation 15.712	—
Phase I: Area Under the Plasma Concentration-time Curve (AUC) AUC Infinity - Day 1	150.0 ng*h/mL Standard Deviation 40.777	156.1 ng*h/mL Standard Deviation 15.497	—
Phase I: Area Under the Plasma Concentration-time Curve (AUC) AUC Infinity - Day 5	136.9 ng*h/mL Standard Deviation 37.897	151.2 ng*h/mL Standard Deviation 17.617	—

SECONDARY outcome

Timeframe: Up to 28 Days of treatment Cycle 1

Population: Full Analysis Set (FAS): 9 participants were included in this set for Phase I

IWG response criteria (2000) - CR: bone marrow evaluations (mCR) show \< 5% blasts; no dysplasia; normal maturation of all cell lines and peripheral blood shows hemoglobin ≥ 11 g/dL; neutrophils ≥ 1,500/mL; platelets ≥ 100,000/mL; 0% blasts; no dysplasia; PR: same as CR, except blasts decrease by ≥ 50% or lower French-American-British (FAB) classification of Myelodysplastic Syndromes; HI: hemoglobin \< 11 g/dL (erythroid); platelet \< 100,000/mL; neutrophils \< 1,000/mL.

Outcome measures

Outcome measures
Measure	Phase II: 20 mg/m2 n=3 Participants 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles	Phase I: 20 mg/m2 n=6 Participants 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of a 4-Week (28-day) Cycle 1	Phase II: 20 mg/m2 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles
Phase I: Number of Participants Who Achieved Complete Remission (CR)+Partial Remission (PR)+Hematological Improvement (HI) - as Per International Working Group (IWG) Response Criteria (2000) PR	1 Participants	1 Participants	—
Phase I: Number of Participants Who Achieved Complete Remission (CR)+Partial Remission (PR)+Hematological Improvement (HI) - as Per International Working Group (IWG) Response Criteria (2000) HI	1 Participants	2 Participants	—

SECONDARY outcome

Timeframe: Up to 1.5 years after the last participant enrolled

Population: 9 participants who achieved remission were evaluated.

Median time required for the participants to achieve remission (complete remission+partial remission).

Outcome measures

Outcome measures
Measure	Phase II: 20 mg/m2 n=9 Participants 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles	Phase I: 20 mg/m2 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of a 4-Week (28-day) Cycle 1	Phase II: 20 mg/m2 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles
Phase II: Median Time to Remission	130.0 Days Interval 67.0 to 208.0	—	—

SECONDARY outcome

Timeframe: Up to 1.5 years after the last participant enrolled

Population: 14 participants who achieved overall improvement were evaluated.

Median time required for the participants to achieve overall improvement (complete remission+partial remission+hematologic improvement)

Outcome measures

Outcome measures
Measure	Phase II: 20 mg/m2 n=14 Participants 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles	Phase I: 20 mg/m2 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of a 4-Week (28-day) Cycle 1	Phase II: 20 mg/m2 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles
Phase II: Median Time to Improvement	26.5 Days Interval 22.0 to 36.0	—	—

SECONDARY outcome

Timeframe: Up to 1.5 years after the last participant enrolled

Population: 9 participants who achieved remission were evaluated.

Median time duration for which participants achieved remission (complete remission+partial remission).

Outcome measures

Outcome measures
Measure	Phase II: 20 mg/m2 n=9 Participants 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles	Phase I: 20 mg/m2 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of a 4-Week (28-day) Cycle 1	Phase II: 20 mg/m2 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles
Phase II: Median Duration of Remission	489 Days Interval 294.0 to 489.0	—	—

SECONDARY outcome

Timeframe: Up to 1.5 years after the last participant enrolled

Population: 14 participants who achieved overall improvement were evaluated.

Median time duration for which participants achieved overall improvement (complete remission+partial remission+hematologic improvement).

Outcome measures

Outcome measures
Measure	Phase II: 20 mg/m2 n=14 Participants 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles	Phase I: 20 mg/m2 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of a 4-Week (28-day) Cycle 1	Phase II: 20 mg/m2 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles
Phase II: Median Duration of Overall Improvement	532 Days Interval 147.0 to 554.0	—	—

SECONDARY outcome

Timeframe: Up to 1.5 years after the last participant enrolled

Population: Full Analysis Set (FAS): 34 participants were included in this set

IWG response criteria (2000) - CR: bone marrow evaluations (mCR) show \< 5% blasts; no dysplasia; normal maturation of all cell lines and peripheral blood shows hemoglobin ≥ 11 g/dL; neutrophils ≥ 1,500/mL; platelets ≥ 100,000/mL; 0% blasts; no dysplasia and PR: same as CR, except blasts decrease by ≥ 50% or lower French-American-British (FAB) classification of Myelodysplastic Syndromes. HI: hemoglobin \< 11 g/dL (erythroid); platelet \< 100,000/mL; neutrophils \< 1,000/mL.

Outcome measures

Outcome measures
Measure	Phase II: 20 mg/m2 n=34 Participants 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles	Phase I: 20 mg/m2 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of a 4-Week (28-day) Cycle 1	Phase II: 20 mg/m2 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles
Phase II: Overall Improvement Rate: Number of Participants Who Achieved Complete Response (CR)+Partial Response (PR)+Hematological Improvement (HI) - as Per International Working Group (IWG) Response Criteria (2000) CR	7 Participants	—	—
Phase II: Overall Improvement Rate: Number of Participants Who Achieved Complete Response (CR)+Partial Response (PR)+Hematological Improvement (HI) - as Per International Working Group (IWG) Response Criteria (2000) PR	2 Participants	—	—
Phase II: Overall Improvement Rate: Number of Participants Who Achieved Complete Response (CR)+Partial Response (PR)+Hematological Improvement (HI) - as Per International Working Group (IWG) Response Criteria (2000) HI	5 Participants	—	—

SECONDARY outcome

Timeframe: Up to 1.5 years after the last participant enrolled

Population: 20 participants who had chromosomal abnormality were evaluated in Phase II for cytogenetic response. The IWG criteria requires 20 analyzable metaphases using conventional cytogenetic techniques.

IWG 2000 - Major: disappearance of cytogenetic abnormality; Minor: 50% or more reduction in abnormal metaphases. IWG 2006 - Complete: disappearance of the chromosomal abnormality without appearance of new ones; Partial: At least 50% reduction of the chromosomal abnormality.

Outcome measures

Outcome measures
Measure	Phase II: 20 mg/m2 n=20 Participants 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles	Phase I: 20 mg/m2 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of a 4-Week (28-day) Cycle 1	Phase II: 20 mg/m2 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles
Phase II: Number of Participants With Cytogenic Response - as Per International Working Group (IWG) Response Criteria 2000 (Major/Minor) and IWG 2006 (Complete/Partial) Major/Complete	6 Participants	—	—
Phase II: Number of Participants With Cytogenic Response - as Per International Working Group (IWG) Response Criteria 2000 (Major/Minor) and IWG 2006 (Complete/Partial) Minor/Partial	1 Participants	—	—
Phase II: Number of Participants With Cytogenic Response - as Per International Working Group (IWG) Response Criteria 2000 (Major/Minor) and IWG 2006 (Complete/Partial) No response	10 Participants	—	—
Phase II: Number of Participants With Cytogenic Response - as Per International Working Group (IWG) Response Criteria 2000 (Major/Minor) and IWG 2006 (Complete/Partial) Not estimable	3 Participants	—	—

Adverse Events

Phase I - 15 mg/m2 Group

Serious events: 1 serious events

Other events: 3 other events

Deaths: 0 deaths

Phase I - 20 mg/m2 Group

Serious events: 1 serious events

Other events: 6 other events

Deaths: 0 deaths

Phase II: 20 mg/m2

Serious events: 11 serious events

Other events: 34 other events

Deaths: 0 deaths

Serious adverse events

Other adverse events

Additional Information

Director

Janssen Pharm KK Japan

Phone: +81-3-4411-5801

Results disclosure agreements

Principal investigator is a sponsor employee
Publication restrictions are in place

Restriction type: GT60

Measure	Phase I - 15 mg/m2 Group n=3 participants at risk 15 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) Cycle 1	Phase I - 20 mg/m2 Group n=6 participants at risk 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) Cycle 1	Phase II: 20 mg/m2 n=34 participants at risk 20 mg/m2 of JNJ-30979754 (decitabine) administered once daily by 1-hour intravenous infusion from Day 1 to 5 of 4-Week (28-day) cycles
Infections and infestations Pneumonia	33.3% 1/3 • Up to 1.5 years after the last participant enrolled	0.00% 0/6 • Up to 1.5 years after the last participant enrolled	11.8% 4/34 • Up to 1.5 years after the last participant enrolled
Infections and infestations Sepsis	0.00% 0/3 • Up to 1.5 years after the last participant enrolled	0.00% 0/6 • Up to 1.5 years after the last participant enrolled	5.9% 2/34 • Up to 1.5 years after the last participant enrolled
Infections and infestations Cellulitis	0.00% 0/3 • Up to 1.5 years after the last participant enrolled	16.7% 1/6 • Up to 1.5 years after the last participant enrolled	2.9% 1/34 • Up to 1.5 years after the last participant enrolled
Infections and infestations Pharyngitis	0.00% 0/3 • Up to 1.5 years after the last participant enrolled	16.7% 1/6 • Up to 1.5 years after the last participant enrolled	2.9% 1/34 • Up to 1.5 years after the last participant enrolled
Infections and infestations Neutropenic infection	0.00% 0/3 • Up to 1.5 years after the last participant enrolled	0.00% 0/6 • Up to 1.5 years after the last participant enrolled	2.9% 1/34 • Up to 1.5 years after the last participant enrolled
Infections and infestations Pneumonia fungal	0.00% 0/3 • Up to 1.5 years after the last participant enrolled	0.00% 0/6 • Up to 1.5 years after the last participant enrolled	2.9% 1/34 • Up to 1.5 years after the last participant enrolled
Infections and infestations Enterocolitis viral	0.00% 0/3 • Up to 1.5 years after the last participant enrolled	0.00% 0/6 • Up to 1.5 years after the last participant enrolled	2.9% 1/34 • Up to 1.5 years after the last participant enrolled
Blood and lymphatic system disorders Febrile neutropenia	0.00% 0/3 • Up to 1.5 years after the last participant enrolled	16.7% 1/6 • Up to 1.5 years after the last participant enrolled	5.9% 2/34 • Up to 1.5 years after the last participant enrolled
Blood and lymphatic system disorders Aneamia	0.00% 0/3 • Up to 1.5 years after the last participant enrolled	0.00% 0/6 • Up to 1.5 years after the last participant enrolled	2.9% 1/34 • Up to 1.5 years after the last participant enrolled
Blood and lymphatic system disorders Neutropenia	0.00% 0/3 • Up to 1.5 years after the last participant enrolled	0.00% 0/6 • Up to 1.5 years after the last participant enrolled	2.9% 1/34 • Up to 1.5 years after the last participant enrolled
Blood and lymphatic system disorders Thrombocytopenia	0.00% 0/3 • Up to 1.5 years after the last participant enrolled	0.00% 0/6 • Up to 1.5 years after the last participant enrolled	2.9% 1/34 • Up to 1.5 years after the last participant enrolled
Nervous system disorders Cerebral infarction	0.00% 0/3 • Up to 1.5 years after the last participant enrolled	0.00% 0/6 • Up to 1.5 years after the last participant enrolled	2.9% 1/34 • Up to 1.5 years after the last participant enrolled
Respiratory, thoracic and mediastinal disorders Pulmonary hypertension	0.00% 0/3 • Up to 1.5 years after the last participant enrolled	0.00% 0/6 • Up to 1.5 years after the last participant enrolled	2.9% 1/34 • Up to 1.5 years after the last participant enrolled
Injury, poisoning and procedural complications Subdural haematoma	0.00% 0/3 • Up to 1.5 years after the last participant enrolled	0.00% 0/6 • Up to 1.5 years after the last participant enrolled	2.9% 1/34 • Up to 1.5 years after the last participant enrolled
Injury, poisoning and procedural complications Wound complication	0.00% 0/3 • Up to 1.5 years after the last participant enrolled	16.7% 1/6 • Up to 1.5 years after the last participant enrolled	2.9% 1/34 • Up to 1.5 years after the last participant enrolled