Trial Outcomes & Findings for Pilot Feasibility Study With Patients Who Are at High Risk For Developing Invasive Candidiasis in a Critical Care Setting (MK-0991-067) (NCT NCT01045798)

Last Updated: 2017-03-24

Results Overview

The feasibility of conducting a major randomized study of caspofungin for empirical therapy for invasive candidiasis in high-risk non-neutropenic intensive care unit (ICU) participants was to be assessed by the incidence of study therapy discontinuations due to investigators choosing to treat participants with empirical antifungal therapy outside of the context of this protocol. Study drug was administered for a minimum of 7 days to a maximum of 14 days provided participants had no evidence of confirmed breakthrough invasive Candida infection while receiving study drug.

Recruitment status

TERMINATED

Study phase

PHASE2

Target enrollment

15 participants

Primary outcome timeframe

1 to 14 days

Results posted on

2017-03-24

Participant Flow

This study was terminated early due to low participant enrollment. One of the 15 participants randomized to treatment inappropriately received a systemic antifungal agent before starting study drug and was not included in the baseline characteristics, safety, or efficacy analyses.

Participant milestones

Participant milestones
Measure	Caspofungin Caspofungin 70 mg caspofungin administered intravenously (IV) on Day 1 followed by 50 mg daily for at least 6 additional days (maximum duration study therapy is 14 days)	Placebo Placebo to caspofungin (normal saline) on Day 1 followed by placebo daily for at least 6 additional days (maximum duration study therapy is 14 days)
Overall Study STARTED	6	9
Overall Study COMPLETED	4	5
Overall Study NOT COMPLETED	2	4

Reasons for withdrawal

Reasons for withdrawal
Measure	Caspofungin Caspofungin 70 mg caspofungin administered intravenously (IV) on Day 1 followed by 50 mg daily for at least 6 additional days (maximum duration study therapy is 14 days)	Placebo Placebo to caspofungin (normal saline) on Day 1 followed by placebo daily for at least 6 additional days (maximum duration study therapy is 14 days)
Overall Study Changed to Open-Label Caspofungin	1	0
Overall Study Invasive Fungal Infection at Baseline	0	1
Overall Study Changed to Other Antifungal Therapy	1	2
Overall Study Received Systemic Antifungal Prestudy	0	1

Baseline Characteristics

Pilot Feasibility Study With Patients Who Are at High Risk For Developing Invasive Candidiasis in a Critical Care Setting (MK-0991-067)

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	Caspofungin n=6 Participants Caspofungin 70 mg caspofungin administered intravenously (IV) on Day 1 followed by 50 mg daily for at least 6 additional days (maximum duration study therapy is 14 days)	Placebo n=8 Participants Placebo to caspofungin (normal saline) on Day 1 followed by placebo daily for at least 6 additional days (maximum duration study therapy is 14 days)	Total n=14 Participants Total of all reporting groups
Age, Continuous	60.2 years STANDARD_DEVIATION 20.1 • n=93 Participants	53.0 years STANDARD_DEVIATION 10.6 • n=4 Participants	56.1 years STANDARD_DEVIATION 15.1 • n=27 Participants
Sex: Female, Male Female	3 Participants n=93 Participants	4 Participants n=4 Participants	7 Participants n=27 Participants
Sex: Female, Male Male	3 Participants n=93 Participants	4 Participants n=4 Participants	7 Participants n=27 Participants

PRIMARY outcome

Timeframe: 1 to 14 days

Population: Of the 114 participants anticipated to enroll in this study, 15 actually enrolled and only 14 received study drug. The participant who did not receive study drug was discontinued; the remaining 14 received at least one dose of study drug, met inclusion/exclusion criteria, and therefore qualified for the full analysis set used for summary analyses.

Outcome measures

Outcome measures
Measure	Caspofungin n=6 Participants Caspofungin 70 mg caspofungin administered intravenously (IV) on Day 1 followed by 50 mg daily for at least 6 additional days (maximum duration study therapy is 14 days)	Placebo n=8 Participants Placebo to caspofungin (normal saline) on Day 1 followed by placebo daily for at least 6 additional days (maximum duration study therapy is 14 days)
The Proportion of Patients Discontinued From Study Therapy to be Treated With Empirical Antifungal Therapy Outside of the Context of the Study.	1 Participants	2 Participants

Adverse Events

Caspofungin

Serious events: 3 serious events

Other events: 4 other events

Deaths: 0 deaths

Placebo

Serious events: 3 serious events

Other events: 6 other events

Deaths: 0 deaths

Serious adverse events

Serious adverse events
Measure	Caspofungin n=6 participants at risk Caspofungin 70 mg caspofungin administered intravenously (IV) on Day 1 followed by 50 mg daily for at least 6 additional days (maximum duration study therapy is 14 days)	Placebo n=8 participants at risk Placebo to caspofungin (normal saline) on Day 1 followed by placebo daily for at least 6 additional days (maximum duration study therapy is 14 days)
Surgical and medical procedures Tracheostomy	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Vascular disorders Hypotension	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Cardiac disorders Cardiac arrest	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Renal and urinary disorders Calculus urethral	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Renal and urinary disorders Renal abscess	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Respiratory, thoracic and mediastinal disorders Pneumonia due to Pseudomonas	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Respiratory, thoracic and mediastinal disorders Respiratory failure	33.3% 2/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.

Other adverse events

Additional Information

Senior Vice President, Global Clinical Development

Merck Sharp & Dohme Corp

Phone: 1-800-672-6372

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee The Sponsor must have the opportunity to review all proposed abstracts, manuscripts, or presentations regarding this study 60 days prior to submission for publication/presentation. Any information identified by the Sponsor as confidential must be deleted prior to submission.
Publication restrictions are in place

Restriction type: OTHER

Measure	Caspofungin n=6 participants at risk Caspofungin 70 mg caspofungin administered intravenously (IV) on Day 1 followed by 50 mg daily for at least 6 additional days (maximum duration study therapy is 14 days)	Placebo n=8 participants at risk Placebo to caspofungin (normal saline) on Day 1 followed by placebo daily for at least 6 additional days (maximum duration study therapy is 14 days)
Blood and lymphatic system disorders Splenomegaly	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Blood and lymphatic system disorders Thrombocytopenia	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Blood and lymphatic system disorders Hyperbilirubinaemia	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Cardiac disorders Bradycardia	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Endocrine disorders Hypoglycaemia	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Gastrointestinal disorders Chronic gastrointestinal bleeding	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Gastrointestinal disorders Colonic obstruction	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Gastrointestinal disorders Diarrhoea	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Gastrointestinal disorders Gastrointestinal bleed	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
General disorders Medical device complication	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Hepatobiliary disorders Hepatic lesion	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Hepatobiliary disorders Hepatic shock	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Hepatobiliary disorders Hepatomegaly	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Infections and infestations Septic shock	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Infections and infestations Sinusitis	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Infections and infestations Urosepsis	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Infections and infestations Vancomycin-resistant enterococcal infection	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Investigations Bilirubin elevated	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Investigations Clostridium difficile toxin test positive	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Investigations Elevated liver enzymes	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Investigations Late diastolic murmur	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Investigations Liver enzyme abnormal	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Metabolism and nutrition disorders Acidosis	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Metabolism and nutrition disorders Hypernatraemia	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Metabolism and nutrition disorders Hypophosphataemia	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Metabolism and nutrition disorders Lactic acidosis	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Nervous system disorders Unresponsive	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Psychiatric disorders Agitation	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Psychiatric disorders Mental status changes	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Respiratory, thoracic and mediastinal disorders Aspiration	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Respiratory, thoracic and mediastinal disorders Bronchoconstriction	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Respiratory, thoracic and mediastinal disorders Hypoxia	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Respiratory, thoracic and mediastinal disorders Pneumonia	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Respiratory, thoracic and mediastinal disorders Pneumonia due to pseudomonas	33.3% 2/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Skin and subcutaneous tissue disorders Decubitus ulcer	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Skin and subcutaneous tissue disorders Ecchymosis	0.00% 0/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	12.5% 1/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Skin and subcutaneous tissue disorders Skin tear	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Vascular disorders Abdominal aortic aneurysm	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Vascular disorders Acute hypotension	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	0.00% 0/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.
Vascular disorders Hypotension	16.7% 1/6 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.	37.5% 3/8 • First dose of study drug through up to 14 days post-treatment All participants who received at least one dose of study drug were included in the safety analyses.