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NCT04848220

A Study Evaluating the Safety, Tolerability, and Effect on Microvascular Obstruction of Intravenous Temanogrel in Adult Participants Undergoing Percutaneous Coronary Intervention

Terminated Phase 2 Results posted Last updated 12 December 2023
What this trial tests

Phase 2 trial testing Temanogrel in Microvascular Obstruction in 29 participants. Terminated before completion.

Timeline
20 May 2021
Primary endpoint
23 August 2022
31 August 2022

Quick facts

Lead sponsorPfizer
PhasePhase 2
StatusTerminated
Study typeINTERVENTIONAL
Allocationrandomized
Designparallel
Maskingdouble
Primary purposetreatment
Enrollment29
Start date20 May 2021
Primary completion23 August 2022
Estimated completion31 August 2022
Sites12 locations across Netherlands, Sweden, United Kingdom, Australia, United States

Drugs / interventions tested

Conditions studied

Sponsor

Pfizer — full company profile →

Who can join

Adults 30 to 80, any sex, with Microvascular Obstruction. Patients with the condition only — healthy volunteers not accepted.

Results — posted to ClinicalTrials.gov

Per-arm endpoint measurements with 95% confidence intervals where reported. Source: trial results section.

Change in Index of Microcirculatory Resistance (IMR) From Baseline to Post Percutaneous Coronary Intervention (PCI) Primary · From Baseline (prior to administration of study treatment) to 15 minutes post-PCI on Day 1

IMR was defined as the mean distal pressure at maximum hyperemia multiplied by the mean hyperemic transit time. IMRcorr (IMR corrected for the influence from collateral supply) was calculated using the following equation, to account for the presence of significant epicardial stenosis without the need for balloon dilation to measure the coronary wedge pressure (Pw), IMRcorr = mean aortic pressure at maximum hyperemia (Pa)\*mean transit time at maximal hyperemia (Tmn) \* \[1.34 \* mean distal coronary pressure at maximum hyperemia (Pd)/Pa minus 0.32\].

GroupValue95% CI
Temanogrel 20 mg-8.1783± 15.35531
Temanogrel 40 mg0.0691± 13.27702
Placebo-1.8907± 18.82659
Change From Baseline to Post-PCI for Coronary Flow Reserve (CFR) Secondary · From Baseline (prior to administration of study treatment) to 15 minutes post-PCI on Day 1

The coronary flow reserve (CFR) was calculated from the ratio of baseline (i.e., resting transit time) to hyperemic mean transit time.

GroupValue95% CI
Temanogrel 20 mg1.2744± 0.89307
Temanogrel 40 mg1.0238± 2.97729
Placebo1.3787± 1.40440
Change From Baseline to Post-PCI for Fractional Flow Reserve (FFR) Secondary · From Baseline (prior to administration of study treatment) to 15 minutes post-PCI on Day 1

The FFR was calculated from the ratio of distal to proximal mean pressures at maximal hyperemia (FFR = \[distal coronary pressure/aortic pressure at maximum hyperemia\]).

GroupValue95% CI
Temanogrel 20 mg0.1346± 0.19620
Temanogrel 40 mg0.2494± 0.20758
Placebo0.3123± 0.16562
Change From Baseline to Post-PCI for Corrected Thrombolysis in Myocardial Infarction Frame Count (cTFC) Secondary · From Baseline (prior to administration of study treatment) to 15 minutes post-PCI on Day 1

The cTFC is a quantitative index of coronary flow and was calculated based upon the number of cine-frames that the intracoronary dye required to reach distal coronary landmarks.

GroupValue95% CI
Temanogrel 20 mg-6.54± 7.365
Temanogrel 40 mg-0.81± 6.320
Placebo-8.93± 8.368
Number of Participants According to Change From Baseline to Post-PCI for Thrombolysis in Myocardial Infarction (TIMI) Flow Grade (TFG) Post-PCI Secondary · Baseline (prior to administration of study treatment) and anytime between 0 to 15 minutes post-PCI on Day 1

The TFG is a measure of epicardial perfusion and was graded on a standard scale from 0 to 3, where Grade 0=no perfusion, grade 1=penetration without perfusion, grade 2=partial perfusion and grade 3= complete perfusion.

Baseline Grade 3
GroupValue95% CI
Temanogrel 20 mg10
Temanogrel 40 mg8
Placebo9
0 to 15 min post-PCI Grade 3
GroupValue95% CI
Temanogrel 20 mg9
Temanogrel 40 mg8
Placebo8
0 to 15 min post-PCI missing
GroupValue95% CI
Temanogrel 20 mg1
Temanogrel 40 mg0
Placebo1
Number of Participants According to Change From Baseline to Post-PCI in Thrombolysis in Myocardial Infarction Myocardial Perfusion Grade (TMPG) Post-PCI Secondary · Baseline (prior to administration of study treatment) and anytime between 0 to 15 minutes post-PCI on Day 1

The TMPG (also known as myocardial blush grade \[MBG\]), is a measure of myocardial perfusion in the capillary bed at the tissues level following contrast injection into the coronary artery. TMPG was graded on a scale from 0 to 3, where grade 0 = failure of dye to enter the microvasculature; grade 1 = dye slowly enters but fails to exit the microvasculature; grade 2 = delayed entry and exit of dye from the microvasculature; grade 3= normal entry and exit of dye from the microvasculature.

Baseline TMPG value 2
GroupValue95% CI
Temanogrel 20 mg1
Temanogrel 40 mg0
Placebo1
Baseline TMPG value 3
GroupValue95% CI
Temanogrel 20 mg7
Temanogrel 40 mg4
Placebo3
Baseline Missing
GroupValue95% CI
Temanogrel 20 mg2
Temanogrel 40 mg4
Placebo5
0 to 15 min post-PCI TMPG value 3
GroupValue95% CI
Temanogrel 20 mg9
Temanogrel 40 mg6
Placebo6
0 to 15 min post-PCI Missing
GroupValue95% CI
Temanogrel 20 mg1
Temanogrel 40 mg2
Placebo3
Change From Baseline to Post-PCI for Creatine Kinase (CK) Secondary · Baseline (prior to administration of study treatment), anytime between 0 to 15 minutes, 6 hours post-PCI, and 24 hours post-PCI/discharge
0 to 15 minutes post-PCI
GroupValue95% CI
Temanogrel 20 mg-11.7± 11.25
Temanogrel 40 mg-6.0± 5.68
Placebo-5.9± 10.58
6 hours post-PCI
GroupValue95% CI
Temanogrel 20 mg0.9± 17.20
Temanogrel 40 mg1.5± 27.07
Placebo-23.5± 41.03
24 hours post- PCI/discharge
GroupValue95% CI
Temanogrel 20 mg-33.7± 23.42
Temanogrel 40 mg233.0± NA
Placebo-6.0± 38.94
Change From Baseline to Post-PCI for Creatine Kinase-Myocardial Band (CK-MB) Secondary · Baseline (prior to administration of study treatment), anytime between 0 to 15 minutes, 6 hours post-PCI and 24 hours post-PCI/discharge
0 to 15 minutes Post-PCI
GroupValue95% CI
Temanogrel 20 mg-0.18± 0.290
Temanogrel 40 mg-0.18± 0.225
Placebo-0.26± 0.490
6 Hours Post-PCI
GroupValue95% CI
Temanogrel 20 mg0.70± 1.260
Temanogrel 40 mg0.79± 2.208
Placebo-0.63± 1.359
24 Hours Post- PCI/Discharge
GroupValue95% CI
Temanogrel 20 mg-0.05± 0.804
Temanogrel 40 mg31.80± NA
Placebo0.97± 0.643
Change From Baseline to Post-PCI for Cardiac Troponin I Secondary · Baseline (prior to administration of study treatment), anytime between 0 to 15 minutes, 6 hours post-PCI and 24 hours post-PCI/discharge
0 to 15 minutes Post-PCI
GroupValue95% CI
Temanogrel 20 mg-0.04± 0.126
Temanogrel 40 mg0.01± 0.035
Placebo0.04± 0.052
6 Hours Post-PCI
GroupValue95% CI
Temanogrel 20 mg0.58± 1.310
Temanogrel 40 mg0.13± 0.354
Placebo0.08± 0.204
24 Hours Post- PCI/Discharge
GroupValue95% CI
Temanogrel 20 mg-0.03± 0.197
Temanogrel 40 mg5.50± NA
Placebo0.30± 0.300
Number of Participants With Procedural Myocardial Injury Secondary · At 6 hours and 24 hours post-PCI/discharge on Day 1

Procedural myocardial injury was defined as elevation of cardiac troponin (cTn) values greater than (\>) 99th percentile upper reference limit (URL) in participants with normal baseline values (\<= 99th percentile URL) or elevation of cTn by \> 20% of the baseline value in participants with elevated cTn levels (\>99th percentile URL).

6 Hours Post-PCI
GroupValue95% CI
Temanogrel 20 mg3
Temanogrel 40 mg1
Placebo1
24 Hours Post-PCI/Discharge
GroupValue95% CI
Temanogrel 20 mg1
Temanogrel 40 mg1
Placebo2
Concentration of Temanogrel Secondary · Pre-PCI, anytime between 0 to 15 minutes,1 hour, 3 hours, 6 hours post-PCI and 24 hours post PCI/discharge

Observed plasma concentration of temanogrel. Lower limit of quantification (LLOQ) of temanogrel was 0.500 nanograms/milliliter (ng/mL).

Pre-PCI
GroupValue95% CI
Temanogrel 20 mg1558.3889± 2156.89423
Temanogrel 40 mg1869.8571± 1815.65878
0 to 15 minutes post PCI
GroupValue95% CI
Temanogrel 20 mg126.9900± 31.08320
Temanogrel 40 mg265.0000± 109.83260
1 hour post PCI
GroupValue95% CI
Temanogrel 20 mg84.8667± 24.45278
Temanogrel 40 mg134.1667± 36.56455
3 hours post PCI
GroupValue95% CI
Temanogrel 20 mg41.8500± 17.23969
Temanogrel 40 mg87.1714± 90.12348
6 hours post PCI
GroupValue95% CI
Temanogrel 20 mg24.6522± 19.78224
Temanogrel 40 mg36.9000± 14.94380
24 hours post-procedure/discharge
GroupValue95% CI
Temanogrel 20 mgNA± NA
Concentration of AR295980 Secondary · Pre-PCI, anytime between 0 to 15 minutes,1 hour, 3 hours, 6 hours post-PCI and 24 hours post PCI/discharge

Observed plasma concentration of AR295980.

Pre-PCI
GroupValue95% CI
Temanogrel 20 mg1.0472± 0.87240
Temanogrel 40 mg3.2010± 3.97562
0 to 15 minutes post PCI
GroupValue95% CI
Temanogrel 20 mg6.3680± 2.61560
Temanogrel 40 mg6.8183± 2.24211
1 hour post PCI
GroupValue95% CI
Temanogrel 20 mg5.0750± 1.81783
Temanogrel 40 mg8.0783± 4.32397
3 hours post PCI
GroupValue95% CI
Temanogrel 20 mg3.6933± 1.18230
Temanogrel 40 mg5.5300± 2.48489
6 hours post PCI
GroupValue95% CI
Temanogrel 20 mg2.4678± 0.79325
Temanogrel 40 mg5.2650± 3.21979
24 hours post-PCI/discharge
GroupValue95% CI
Temanogrel 20 mg0.3518± 0.40765

Adverse events — posted to ClinicalTrials.gov

Time frame: From start of study treatment on Day 1 to up to maximum of 10 days. Reporting threshold: 0%. Adverse-event reports describe events observed during the trial — not all are caused by the drug.

Temanogrel 20 mg
Serious: 0/10 (0%)
Deaths: 0/10
Temanogrel 40 mg
Serious: 2/8 (25%)
Deaths: 0/8
Placebo
Serious: 1/9 (11%)
Deaths: 0/9

Serious adverse events (3 terms)

ReactionSystemTemanogrel 20 mgTemanogrel 40 mgPlacebo
Vascular access site haematomaInjury, poisoning and procedural complications
Aortic dissectionVascular disorders
Acute myocardial infarctionCardiac disorders
Other adverse events (20 terms — click to expand)

ReactionSystemTemanogrel 20 mgTemanogrel 40 mgPlacebo
Vascular access site haematomaInjury, poisoning and procedural complications
HypertensionVascular disorders
Atrial fibrillationCardiac disorders
Atrioventricular block second degreeCardiac disorders
Cardiac arrestCardiac disorders
Cardiogenic shockCardiac disorders
Coronary artery dissectionCardiac disorders
NauseaGastrointestinal disorders
Non-cardiac chest painGeneral disorders
Oedema peripheralGeneral disorders
Congestive hepatopathyHepatobiliary disorders
Procedural painInjury, poisoning and procedural complications
Blood alkaline phosphatase increasedInvestigations
Blood bilirubin increasedInvestigations
Transaminases increasedInvestigations
Back painMusculoskeletal and connective tissue disorders
HeadacheNervous system disorders
Acute kidney injuryRenal and urinary disorders
Respiratory failureRespiratory, thoracic and mediastinal disorders
Aortic dissectionVascular disorders

Most-reported serious reactions: Vascular access site haematoma, Aortic dissection, Acute myocardial infarction.

Data from ClinicalTrials.gov NCT04848220 adverse events section.

Sponsor's own description

The purpose of this study is to determine whether intravenous temanogrel is a safe and effective treatment for microvascular obstruction (MVO) in adult participants undergoing percutaneous coronary intervention (PCI).

Publications & conference data

1 peer-reviewed publication reference this trial (live from Europe PMC):

  1. Acute Coronary Syndromes (ACS)-Unravelling Biology to Identify New Therapies-The Microcirculation as a Frontier for New Therapies in ACS.
    Vaidya K, Tucker B, Patel S, Ng MKC. · · 2021 · cited 8× · PMID 34571836 · DOI 10.3390/cells10092188

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Other trials of Temanogrel

Trials testing the same drug.

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Trials by the same sponsor.

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Drug Landscape aggregates and links these public records for informational use only. Always verify against the primary source before clinical or regulatory decisions. Canonical URL: https://druglandscape.com/trial/NCT04848220.

Primary sources · FDA · ClinicalTrials.gov · EMA · SEC EDGAR · ChEMBL · Wikidata · full sourcing